Targeting transcription factor NF-κB to overcome chemoresistance and radioresistance in cancer therapy

Biochimica et Biophysica Acta - Reviews on Cancer

Volumn 1805, Issue 2, 2010, Pages 167-180

  Li, Feng ^a   Sethi, Gautam ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

Apoptosis; Cancer; Chemoresistance; NF B; Radioresistance

Indexed keywords

2 AMINO 6 BROMO 4 (1 CYANO 2 ETHOXY 2 OXOETHYL) 4H CHROMENE 3 CARBOXYLIC ACID ETHYL ESTER; 4 [5 (4 CHLOROPHENYL) 3 TRIFLUOROMETHYL 1H PYRAZOL 1 YL]BENZENESULFONAMIDE; ANTINEOPLASTIC AGENT; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BORTEZOMIB; CAMPTOTHECIN; CARBOPLATIN; CELECOXIB; CISPLATIN; DACTINOMYCIN; DAUNORUBICIN; DOCETAXEL; DOXORUBICIN; EPOXOMICIN; ETOPOSIDE; FLUOROURACIL; GEMCITABINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRINOTECAN; MELPHALAN; MITOXANTRONE; N (2 CYCLOHEXYLOXY 4 NITROPHENYL)METHANESULFONAMIDE; OBLIMERSEN; PACLITAXEL; SHORT HAIRPIN RNA; TAMOXIFEN; TAXANE DERIVATIVE; UNINDEXED DRUG; VINBLASTINE; VINCRISTINE;

ANTINEOPLASTIC ACTIVITY; CANCER RADIOTHERAPY; CANCER RESISTANCE; CLINICAL TRIAL; CYTOTOXICITY; DRUG POTENTIATION; DRUG SELECTIVITY; DRUG SENSITIVITY; DRUG TARGETING; GENE CONTROL; HUMAN; IONIZING RADIATION; LUNG ADENOCARCINOMA; MULTIPLE MYELOMA; NEOPLASM; NONHUMAN; OVARY CARCINOMA; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; PROSTATECTOMY; RADIATION EXPOSURE; RADIATION RESPONSE; RADIOSENSITIVITY; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; NF-KAPPA B; RADIATION TOLERANCE;

EID: 77649341172     PISSN: 0304419X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbcan.2010.01.002     Document Type: Review

References (241)

1. Sethi G., and Tergaonkar V. Potential pharmacological control of the NF-kappaB pathway. Trends Pharmacol. Sci. 30 (2009) 313-321
2. Sethi G., Sung B., and Aggarwal B.B. Nuclear factor-kappaB activation: from bench to bedside. Exp. Biol. Med. (Maywood) 233 (2008) 21-31
3. Vallabhapurapu S., and Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu. Rev. Immunol. 27 (2009) 693-733
4. Shen H.M., and Tergaonkar V. NFkappaB signaling in carcinogenesis and as a potential molecular target for cancer therapy. Apoptosis 14 (2009) 348-363
5. Aggarwal B.B., Vijayalekshmi R.V., and Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin. Cancer Res. 15 (2009) 425-430
6. Baud V., and Karin M. Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat. Rev. Drug Discov. 8 (2009) 33-40
7. Cusack J.C., Liu R., and Baldwin A.S. NF- kappa B and chemoresistance: potentiation of cancer drugs via inhibition of NF- kappa B. Drug Resist. Updat. 2 (1999) 271-273
8. Nakanishi C., and Toi M. Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nat. Rev., Cancer 5 (2005) 297-309
9. Campbell K.J., O'Shea J.M., and Perkins N.D. Differential regulation of NF-kappaB activation and function by topoisomerase II inhibitors. BMC Cancer 6 (2006) 101
10. Melisi D., and Chiao P.J. NF-kappa B as a target for cancer therapy. Expert Opin. Ther. Targets 11 (2007) 133-144
11. Baumann P., Mandl-Weber S., Oduncu F., and Schmidmaier R. Alkylating agents induce activation of NFkappaB in multiple myeloma cells. Leuk. Res. 32 (2008) 1144-1147
12. Bednarski B.K., Ding X., Coombe K., Baldwin A.S., and Kim H.J. Active roles for inhibitory kappaB kinases alpha and beta in nuclear factor-kappaB-mediated chemoresistance to doxorubicin. Mol. Cancer Ther. 7 (2008) 1827-1835
13. Konstantinopoulos P.A., Fountzilas E., Pillay K., Zerbini L.F., Libermann T.A., Cannistra S.A., and Spentzos D. Carboplatin-induced gene expression changes in vitro are prognostic of survival in epithelial ovarian cancer. BMC Med. Genomics 1 (2008) 59
14. Bottero V., Busuttil V., Loubat A., Magne N., Fischel J.L., Milano G., and Peyron J.F. Activation of nuclear factor kappaB through the IKK complex by the topoisomerase poisons SN38 and doxorubicin: a brake to apoptosis in HeLa human carcinoma cells. Cancer Res. 61 (2001) 7785-7791
15. Wu Z.H., Shi Y., Tibbetts R.S., and Miyamoto S. Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science 311 (2006) 1141-1146
16. Piret B., Schoonbroodt S., and Piette J. The ATM protein is required for sustained activation of NF-kappaB following DNA damage. Oncogene 18 (1999) 2261-2271
17. Li N., Banin S., Ouyang H., Li G.C., Courtois G., Shiloh Y., Karin M., and Rotman G. ATM is required for IkappaB kinase (IKKk) activation in response to DNA double strand breaks. J. Biol. Chem. 276 (2001) 8898-8903
18. Piret B., and Piette J. Topoisomerase poisons activate the transcription factor NF-kappaB in ACH-2 and CEM cells. Nucleic Acids Res. 24 (1996) 4242-4248
19. Das K.C., and White C.W. Activation of NF-kappaB by antineoplastic agents. Role of protein kinase C. J. Biol. Chem. 272 (1997) 14914-14920
20. Andriollo M., Favier A., and Guiraud P. Adriamycin activates NF-kappaB in human lung carcinoma cells by IkappaBalpha degradation. Arch. Biochem. Biophys. 413 (2003) 75-82
21. Tergaonkar V., Pando M., Vafa O., Wahl G., and Verma I. p53 stabilization is decreased upon NFkappaB activation: a role for NFkappaB in acquisition of resistance to chemotherapy. Cancer Cells 1 (2002) 493-503
22. Tergaonkar V., Bottero V., Ikawa M., Li Q., and Verma I.M. IkappaB kinase-independent IkappaBalpha degradation pathway: functional NF-kappaB activity and implications for cancer therapy. Mol. Cell. Biol. 23 (2003) 8070-8083
23. Janssens S., Tinel A., Lippens S., and Tschopp J. PIDD mediates NF-kappaB activation in response to DNA damage. Cell 123 (2005) 1079-1092
24. Mabb A.M., Wuerzberger-Davis S.M., and Miyamoto S. PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress. Nat. Cell Biol. 8 (2006) 986-993
25. Rosette C., and Karin M. Cytoskeletal control of gene expression: depolymerization of microtubules activates NF-kappa B. J. Cell Biol. 128 (1995) 1111-1119
26. Huang Y., Johnson K.R., Norris J.S., and Fan W. Nuclear factor-kappaB/IkappaB signaling pathway may contribute to the mediation of paclitaxel-induced apoptosis in solid tumor cells. Cancer Res. 60 (2000) 4426-4432
27. Dong Q.G., Sclabas G.M., Fujioka S., Schmidt C., Peng B., Wu T., Tsao M.S., Evans D.B., Abbruzzese J.L., McDonnell T.J., and Chiao P.J. The function of multiple IkappaB : NF-kappaB complexes in the resistance of cancer cells to Taxol-induced apoptosis. Oncogene 21 (2002) 6510-6519
28. Zemskova M., Sahakian E., Bashkirova S., and Lilly M. The PIM1 kinase is a critical component of a survival pathway activated by docetaxel and promotes survival of docetaxel-treated prostate cancer cells. J. Biol. Chem. 283 (2008) 20635-20644
29. Giri D.K., Pantazis P., and Aggarwal B.B. Cellular resistance to vincristine suppresses NF-kappa B activation and apoptosis but enhances c-Jun-NH2-terminal protein kinase activation by tumor necrosis. Apoptosis 4 (1999) 291-301
30. Sanchez-Perez I., Benitah S.A., Martinez-Gomariz M., Lacal J.C., and Perona R. Cell stress and MEKK1-mediated c-Jun activation modulate NFkappaB activity and cell viability. Mol. Biol. Cell 13 (2002) 2933-2945
31. Yeh P.Y., Chuang S.E., Yeh K.H., Song Y.C., Ea C.K., and Cheng A.L. Increase of the resistance of human cervical carcinoma cells to cisplatin by inhibition of the MEK to ERK signaling pathway partly via enhancement of anticancer drug-induced NF kappa B activation. Biochem. Pharmacol. 63 (2002) 1423-1430
32. Campbell K.J., Witty J.M., Rocha S., and Perkins N.D. Cisplatin mimics ARF tumor suppressor regulation of RelA (p65) nuclear factor-kappaB transactivation. Cancer Res. 66 (2006) 929-935
33. Uetsuka H., Haisa M., Kimura M., Gunduz M., Kaneda Y., Ohkawa T., Takaoka M., Murata T., Nobuhisa T., Yamatsuji T., Matsuoka J., Tanaka N., and Naomoto Y. Inhibition of inducible NF-kappaB activity reduces chemoresistance to 5-fluorouracil in human stomach cancer cell line. Exp. Cell Res. 289 (2003) 27-35
34. Wang W., McLeod H.L., and Cassidy J. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int. J. Cancer 104 (2003) 504-511
35. Wang W., and Cassidy J. Constitutive nuclear factor-kappa B mRNA, protein overexpression and enhanced DNA-binding activity in thymidylate synthase inhibitor-resistant tumour cells. Br. J. Cancer 88 (2003) 624-629
36. Fukuyama R., Ng K.P., Cicek M., Kelleher C., Niculaita R., Casey G., and Sizemore N. Role of IKK and oscillatory NFkappaB kinetics in MMP-9 gene expression and chemoresistance to 5-fluorouracil in RKO colorectal cancer cells. Mol. Carcinog. 46 (2007) 402-413
37. Arlt A., Gehrz A., Muerkoster S., Vorndamm J., Kruse M.L., Folsch U.R., and Schafer H. Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene 22 (2003) 3243-3251
38. Dolcet X., Llobet D., Encinas M., Pallares J., Cabero A., Schoenenberger J.A., Comella J.X., and Matias-Guiu X. Proteasome inhibitors induce death but activate NF-kappaB on endometrial carcinoma cell lines and primary culture explants. J. Biol. Chem. 281 (2006) 22118-22130
39. Brach M.A., Hass R., Sherman M.L., Gunji H., Weichselbaum R., and Kufe D. Ionizing radiation induces expression and binding activity of the nuclear factor kappa B. J. Clin. Invest. 88 (1991) 691-695
40. Basu S., Rosenzweig K.R., Youmell M., and Price B.D. The DNA-dependent protein kinase participates in the activation of NF kappa B following DNA damage. Biochem. Biophys. Res. Commun. 247 (1998) 79-83
41. Lee S.J., Dimtchev A., Lavin M.F., Dritschilo A., and Jung M. A novel ionizing radiation-induced signaling pathway that activates the transcription factor NF-kappaB. Oncogene 17 (1998) 1821-1826
42. Li N., and Karin M. Ionizing radiation and short wavelength UV activate NF-kappaB through two distinct mechanisms. Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 13012-13017
43. Zhou D., Brown S.A., Yu T., Chen G., Barve S., Kang B.C., and Thompson J.S. A high dose of ionizing radiation induces tissue-specific activation of nuclear factor-kappaB in vivo. Radiat. Res. 151 (1999) 703-709
44. Chen X., Shen B., Xia L., Khaletzkiy A., Chu D., Wong J.Y., and Li J.J. Activation of nuclear factor kappaB in radioresistance of TP53-inactive human keratinocytes. Cancer Res. 62 (2002) 1213-1221
45. Criswell T., Leskov K., Miyamoto S., Luo G., and Boothman D.A. Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation. Oncogene 22 (2003) 5813-5827
46. Rodel F., Hantschel M., Hildebrandt G., Schultze-Mosgau S., Rodel C., Herrmann M., Sauer R., and Voll R.E. Dose-dependent biphasic induction and transcriptional activity of nuclear factor kappa B (NF-kappaB) in EA.hy.926 endothelial cells after low-dose X-irradiation. Int. J. Radiat. Biol. 80 (2004) 115-123
47. Rithidech K.N., Tungjai M., Arbab E., and Simon S.R. Activation of NF-kappaB in bone marrow cells of BALB/cJ mice following exposure in vivo to low doses of (137)Cs gamma-rays. Radiat. Environ. Biophys. 44 (2005) 139-143
48. Ahmed K.M., Dong S., Fan M., and Li J.J. Nuclear factor-kappaB p65 inhibits mitogen-activated protein kinase signaling pathway in radioresistant breast cancer cells. Mol. Cancer Res. 4 (2006) 945-955
49. Natarajan M., Nayak B.K., Galindo C., Mathur S.P., Roldan F.N., and Meltz M.L. Nuclear translocation and DNA-binding activity of NFKB (NF-kappaB) after exposure of human monocytes to pulsed ultra-wideband electromagnetic fields (1 kV/cm) fails to transactivate kappaB-dependent gene expression. Radiat. Res. 165 (2006) 645-654
50. Lewis D.A., and Spandau D.F. UVB activation of NF-kappaB in normal human keratinocytes occurs via a unique mechanism. Arch. Dermatol. Res. 299 (2007) 93-101
51. Laszlo C.F., and Wu S. Mechanism of UV-induced IkappaBalpha-independent activation of NF-kappaB. Photochem. Photobiol. 84 (2008) 1564-1568
52. Cao N., Li S., Wang Z., Ahmed K.M., Degnan M.E., Fan M., Dynlacht J.R., and Li J.J. NF-kappaB-mediated HER2 overexpression in radiation-adaptive resistance. Radiat. Res. 171 (2009) 9-21
53. Veuger S.J., Hunter J.E., and Durkacz B.W. Ionizing radiation-induced NF-kappaB activation requires PARP-1 function to confer radioresistance. Oncogene 28 (2009) 832-842
54. Yakovlev V.A., Barani I.J., Rabender C.S., Black S.M., Leach J.K., Graves P.R., Kellogg G.E., and Mikkelsen R.B. Tyrosine nitration of IkappaBalpha: a novel mechanism for NF-kappaB activation. Biochemistry 46 (2007) 11671-11683
55. Bender K., Gottlicher M., Whiteside S., Rahmsdorf H.J., and Herrlich P. Sequential DNA damage-independent and -dependent activation of NF-kappaB by UV. EMBO J. 17 (1998) 5170-5181
56. Lewis D.A., and Spandau D.F. UVB-induced activation of NF-kappaB is regulated by the IGF-1R and dependent on p38 MAPK. J. Invest. Dermatol. 128 (2008) 1022-1029
57. Yoshida K., Sasaki R., Nishimura H., Okamoto Y., Suzuki Y., Kawabe T., Saito M., Otsuki N., Hayashi Y., Soejima T., Nibu K., and Sugimura K. Nuclear factor-kappaB expression as a novel marker of radioresistance in early-stage laryngeal cancer. Head Neck (2009)
58. Yamamoto K., Arakawa T., Ueda N., and Yamamoto S. Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. J. Biol. Chem. 270 (1995) 31315-31320
59. Guttridge D.C., Albanese C., Reuther J.Y., Pestell R.G., and Baldwin Jr. A.S. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell. Biol. 19 (1999) 5785-5799
60. Catz S.D., and Johnson J.L. Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene 20 (2001) 7342-7351
61. Tamatani M., Che Y.H., Matsuzaki H., Ogawa S., Okado H., Miyake S., Mizuno T., and Tohyama M. Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons. J. Biol. Chem. 274 (1999) 8531-8538
62. Zhu L., Fukuda S., Cordis G., Das D.K., and Maulik N. Anti-apoptotic protein survivin plays a significant role in tubular morphogenesis of human coronary arteriolar endothelial cells by hypoxic preconditioning. FEBS Lett. 508 (2001) 369-374
63. Stehlik C., de Martin R., Kumabashiri I., Schmid J.A., Binder B.R., and Lipp J. Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J. Exp. Med. 188 (1998) 211-216
64. Kumar A., Takada Y., Boriek A.M., and Aggarwal B.B. Nuclear factor-kappaB: its role in health and disease. J. Mol. Med. 82 (2004) 434-448
65. Wong E.T., and Tergaonkar V. Roles of NF-kappaB in health and disease: mechanisms and therapeutic potential. Clin. Sci. (Lond) 116 (2009) 451-465
66. Sethi G., Ahn K.S., Chaturvedi M.M., and Aggarwal B.B. Epidermal growth factor (EGF) activates nuclear factor-kappaB through IkappaBalpha kinase-independent but EGF receptor-kinase dependent tyrosine 42 phosphorylation of IkappaBalpha. Oncogene 26 (2007) 7324-7332
67. Sethi G., Ahn K.S., Sung B., Kunnumakkara A.B., Chaturvedi M.M., and Aggarwal B.B. SH-5, an AKT inhibitor potentiates apoptosis and inhibits invasion through the suppression of anti-apoptotic, proliferative and metastatic gene products regulated by IkappaBalpha kinase activation. Biochem. Pharmacol. 76 (2008) 1404-1416
68. Dannenberg A.J., and Subbaramaiah K. Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cells 4 (2003) 431-436
69. Subbaramaiah K., Hart J.C., Norton L., and Dannenberg A.J. Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2 AND p38 mitogen-activated protein kinase pathways. J. Biol. Chem. 275 (2000) 14838-14845
70. Subbaramaiah K., Marmo T.P., Dixon D.A., and Dannenberg A.J. Regulation of cyclooxgenase-2 mRNA stability by taxanes: evidence for involvement of p38, MAPKAPK-2, and HuR. J. Biol. Chem. 278 (2003) 37637-37647
71. Trifan O.C., Durham W.F., Salazar V.S., Horton J., Levine B.D., Zweifel B.S., Davis T.W., and Masferrer J.L. Cyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11. Cancer Res. 62 (2002) 5778-5784
72. L'Esperance S., Popa I., Bachvarova M., Plante M., Patten N., Wu L., Tetu B., and Bachvarov D. Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors. Int. J. Oncol. 29 (2006) 5-24
73. Singh B., Cook K.R., Vincent L., Hall C.S., Berry J.A., Multani A.S., and Lucci A. Cyclooxygenase-2 induces genomic instability, BCL2 expression, doxorubicin resistance, and altered cancer-initiating cell phenotype in MCF7 breast cancer cells. J. Surg. Res. 147 (2008) 240-246
74. Wang R., Wang X., Lin F., Gao P., Dong K., and Zhang H.Z. shRNA-targeted cyclooxygenase (COX)-2 inhibits proliferation, reduces invasion and enhances chemosensitivity in laryngeal carcinoma cells. Mol. Cell. Biochem. 317 (2008) 179-188
75. Gaffney D.K., Holden J., Davis M., Zempolich K., Murphy K.J., and Dodson M. Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 49 (2001) 1213-1217
76. Terakado N., Shintani S., Yano J., Chunnan L., Mihara M., Nakashiro K., and Hamakawa H. Overexpression of cyclooxygenase-2 is associated with radioresistance in oral squamous cell carcinoma. Oral Oncol. 40 (2004) 383-389
77. Chen W.C., McBride W.H., Chen S.M., Lee K.F., Hwang T.Z., Jung S.M., Shau H., Liao S.K., Hong J.H., and Chen M.F. Prediction of poor survival by cyclooxygenase-2 in patients with T4 nasopharyngeal cancer treated by radiation therapy: clinical and in vitro studies. Head Neck 27 (2005) 503-512
78. Dittmann K.H., Mayer C., Ohneseit P.A., Raju U., Andratschke N.H., Milas L., and Rodemann H.P. Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair: a COX-2 independent mechanism. Int. J. Radiat. Oncol. Biol. Phys. 70 (2008) 203-212
79. Wildeman M.A., Gibcus J.H., Hauptmann M., Begg A.C., van Velthuysen M.L., Hoebers F.J., Mastik M.F., Schuuring E., van der Wal J.E., and van den Brekel M.W. Radiotherapy in laryngeal carcinoma: can a panel of 13 markers predict response?. Laryngoscope 119 (2009) 316-322
80. Kishi K., Petersen S., Petersen C., Hunter N., Mason K., Masferrer J.L., Tofilon P.J., and Milas L. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res. 60 (2000) 1326-1331
81. Nakata E., Mason K.A., Hunter N., Husain A., Raju U., Liao Z., Ang K.K., and Milas L. Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors. Int. J. Radiat. Oncol. Biol. Phys. 58 (2004) 369-375
82. Karim A., McCarthy K., Jawahar A., Smith D., Willis B., and Nanda A. Differential cyclooxygenase-2 enzyme expression in radiosensitive versus radioresistant glioblastoma multiforme cell lines. Anticancer Res. 25 (2005) 675-679
83. Gansauge S., Gansauge F., Ramadani M., Stobbe H., Rau B., Harada N., and Beger H.G. Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis. Cancer Res. 57 (1997) 1634-1637
84. Biliran Jr. H., Wang Y., Banerjee S., Xu H., Heng H., Thakur A., Bollig A., Sarkar F.H., and Liao J.D. Overexpression of cyclin D1 promotes tumor cell growth and confers resistance to cisplatin-mediated apoptosis in an elastase-myc transgene-expressing pancreatic tumor cell line. Clin. Cancer Res. 11 (2005) 6075-6086
85. Ahmed K.M., Fan M., Nantajit D., Cao N., and Li J.J. Cyclin D1 in low-dose radiation-induced adaptive resistance. Oncogene 27 (2008) 6738-6748
86. Kim J.K., and Diehl J.A. Nuclear cyclin D1: an oncogenic driver in human cancer. J. Cell. Physiol. 220 (2009) 292-296
87. Kornmann M., Danenberg K.D., Arber N., Beger H.G., Danenberg P.V., and Korc M. Inhibition of cyclin D1 expression in human pancreatic cancer cells is associated with increased chemosensitivity and decreased expression of multiple chemoresistance genes. Cancer Res. 59 (1999) 3505-3511
88. Kornmann M., Arber N., and Korc M. Inhibition of basal and mitogen-stimulated pancreatic cancer cell growth by cyclin D1 antisense is associated with loss of tumorigenicity and potentiation of cytotoxicity to cisplatinum. J. Clin. Invest. 101 (1998) 344-352
89. Coco Martin J.M., Balkenende A., Verschoor T., Lallemand F., and Michalides R. Cyclin D1 overexpression enhances radiation-induced apoptosis and radiosensitivity in a breast tumor cell line. Cancer Res. 59 (1999) 1134-1140
90. Milas L., Akimoto T., Hunter N.R., Mason K.A., Buchmiller L., Yamakawa M., Muramatsu H., and Ang K.K. Relationship between cyclin D1 expression and poor radioresponse of murine carcinomas. Int. J. Radiat. Oncol. Biol. Phys. 52 (2002) 514-521
91. Cordes N. Overexpression of hyperactive integrin-linked kinase leads to increased cellular radiosensitivity. Cancer Res. 64 (2004) 5683-5692
92. Dixon E.P., Stephenson D.T., Clemens J.A., and Little S.P. Bcl-Xshort is elevated following severe global ischemia in rat brains. Brain Res. 776 (1997) 222-229
93. Amundson S.A., Myers T.G., Scudiero D., Kitada S., Reed J.C., and Fornace Jr. A.J. An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res. 60 (2000) 6101-6110
94. Zhu C.J., Li Y.B., and Wong M.C. Expression of antisense bcl-2 cDNA abolishes tumorigenicity and enhances chemosensitivity of human malignant glioma cells. J. Neurosci. Res. 74 (2003) 60-66
95. Hopkins-Donaldson S., Cathomas R., Simoes-Wust A.P., Kurtz S., Belyanskaya L., Stahel R.A., and Zangemeister-Wittke U. Induction of apoptosis and chemosensitization of mesothelioma cells by Bcl-2 and Bcl-xL antisense treatment. Int. J. Cancer 106 (2003) 160-166
96. Tolcher A.W., Chi K., Kuhn J., Gleave M., Patnaik A., Takimoto C., Schwartz G., Thompson I., Berg K., D'Aloisio S., Murray N., Frankel S.R., Izbicka E., and Rowinsky E. A phase II, pharmacokinetic, and biological correlative study of oblimersen sodium and docetaxel in patients with hormone-refractory prostate cancer. Clin. Cancer Res. 11 (2005) 3854-3861
97. Bolenz C., Becker A., Trojan L., Schaaf A., Cao Y., Weiss C., Alken P., and Michel M.S. Optimizing chemotherapy for transitional cell carcinoma by application of Bcl-2 and Bcl-xL antisense oligodeoxynucleotides. Urol. Oncol. 25 (2007) 476-482
98. Arisan E.D., Kutuk O., Tezil T., Bodur C., Telci D., and Basaga H. Small inhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect of cisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancer cells. Breast Cancer Res. Treat. 119 (2010) 271-281
99. Trask D.K., Wolf G.T., Bradford C.R., Fisher S.G., Devaney K., Johnson M., Singleton T., and Wicha M. Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ preservation. Laryngoscope 112 (2002) 638-644
100. Kim D.W., Kim K.O., Shin M.J., Ha J.H., Seo S.W., Yang J., and Lee F.Y. siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells. Mol. Cancer 8 (2009) 28
101. Zhan Q., Alamo I., Yu K., Boise L.H., Cherney B., Tosato G., O'Connor P.M., and Fornace Jr. A.J. The apoptosis-associated gamma-ray response of BCL-X(L) depends on normal p53 function. Oncogene 13 (1996) 2287-2293
102. Lee J.U., Hosotani R., Wada M., Doi R., Kosiba T., Fujimoto K., Miyamoto Y., Tsuji S., Nakajima S., Nishimura Y., and Imamura M. Role of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-X) on cellular susceptibility to radiation in pancreatic cancer cells. Eur. J. Cancer 35 (1999) 1374-1380
103. Rosser C.J., Reyes A.O., Vakar-Lopez F., Levy L.B., Kuban D.A., Hoover D.C., Lee A.K., and Pisters L.L. Bcl-2 is significantly overexpressed in localized radio-recurrent prostate carcinoma, compared with localized radio-naive prostate carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 56 (2003) 1-6
104. Nix P., Cawkwell L., Patmore H., Greenman J., and Stafford N. Bcl-2 expression predicts radiotherapy failure in laryngeal cancer. Br. J. Cancer 92 (2005) 2185-2189
105. An J., Chervin A.S., Nie A., Ducoff H.S., and Huang Z. Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor. Oncogene 26 (2007) 652-661
106. Kim D.W., Seo S.W., Cho S.K., Chang S.S., Lee H.W., Lee S.E., Block J.A., Hei T.K., and Lee F.Y. Targeting of cell survival genes using small interfering RNAs (siRNAs) enhances radiosensitivity of Grade II chondrosarcoma cells. J. Orthop. Res. 25 (2007) 820-828
107. Mita A.C., Mita M.M., Nawrocki S.T., and Giles F.J. Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin. Cancer Res. 14 (2008) 5000-5005
108. Kawakami H., Tomita M., Matsuda T., Ohta T., Tanaka Y., Fujii M., Hatano M., Tokuhisa T., and Mori N. Transcriptional activation of survivin through the NF-kappaB pathway by human T-cell leukemia virus type I tax. Int. J. Cancer 115 (2005) 967-974
109. Ikeguchi M., and Kaibara N. Changes in survivin messenger RNA level during cisplatin treatment in gastric cancer. Int. J. Mol. Med. 8 (2001) 661-666
110. Tran J., Master Z., Yu J.L., Rak J., Dumont D.J., and Kerbel R.S. A role for survivin in chemoresistance of endothelial cells mediated by VEGF. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 4349-4354
111. Als A.B., Dyrskjot L., von der Maase H., Koed K., Mansilla F., Toldbod H.E., Jensen J.L., Ulhoi B.P., Sengelov L., Jensen K.M., and Orntoft T.F. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. Clin. Cancer Res. 13 (2007) 4407-4414
112. Hinnis A.R., Luckett J.C., and Walker R.A. Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients. Br. J. Cancer 96 (2007) 639-645
113. Nakagawa Y., Abe S., Kurata M., Hasegawa M., Yamamoto K., Inoue M., Takemura T., Suzuki K., and Kitagawa M. IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes. Am. J. Hematol. 81 (2006) 824-831
114. Schlette E.J., Medeiros L.J., Goy A., Lai R., and Rassidakis G.Z. Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma. J. Clin. Oncol. 22 (2004) 1682-1688
115. Kleinberg L., Florenes V.A., Silins I., Haug K., Trope C.G., Nesland J.M., and Davidson B. Nuclear expression of survivin is associated with improved survival in metastatic ovarian carcinoma. Cancer 109 (2007) 228-238
116. Nomura T., Yamasaki M., Nomura Y., and Mimata H. Expression of the inhibitors of apoptosis proteins in cisplatin-resistant prostate cancer cells. Oncol. Rep. 14 (2005) 993-997
117. Virrey J.J., Guan S., Li W., Schonthal A.H., Chen T.C., and Hofman F.M. Increased survivin expression confers chemoresistance to tumor-associated endothelial cells. Am. J. Pathol. 173 (2008) 575-585
118. Wang T., Wei J., Qian X., Ding Y., Yu L., and Liu B. Gambogic acid, a potent inhibitor of survivin, reverses docetaxel resistance in gastric cancer cells. Cancer Lett. 262 (2008) 214-222
119. Asanuma K., Moriai R., Yajima T., Yagihashi A., Yamada M., Kobayashi D., and Watanabe N. Survivin as a radioresistance factor in pancreatic cancer. Jpn. J. Cancer Res. 91 (2000) 1204-1209
120. Pennati M., Binda M., Colella G., Folini M., Citti L., Villa R., Daidone M.G., and Zaffaroni N. Radiosensitization of human melanoma cells by ribozyme-mediated inhibition of survivin expression. J. Invest. Dermatol. 120 (2003) 648-654
121. Cao C., Mu Y., Hallahan D.E., and Lu B. XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer. Oncogene 23 (2004) 7047-7052
122. Rodel F., Hoffmann J., Distel L., Herrmann M., Noisternig T., Papadopoulos T., Sauer R., and Rodel C. Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res. 65 (2005) 4881-4887
123. McLaughlin N., Annabi B., Bouzeghrane M., Temme A., Bahary J.P., Moumdjian R., and Beliveau R. The Survivin-mediated radioresistant phenotype of glioblastomas is regulated by RhoA and inhibited by the green tea polyphenol (-)-epigallocatechin-3-gallate. Brain Res. 1071 (2006) 1-9
124. Yu H.G., Ai Y.W., Yu L.L., Zhou X.D., Liu J., Li J.H., Xu X.M., Liu S., Chen J., Liu F., Qi Y.L., Deng Q., Cao J., Liu S.Q., Luo H.S., and Yu J.P. Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death. Int. J. Cancer 122 (2008) 433-443
125. Saito T., Hama S., Izumi H., Yamasaki F., Kajiwara Y., Matsuura S., Morishima K., Hidaka T., Shrestha P., Sugiyama K., and Kurisu K. Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells. Br. J. Cancer 98 (2008) 345-355
126. Yang C.T., Li J.M., Weng H.H., Li Y.C., Chen H.C., and Chen M.F. Adenovirus-mediated transfer of siRNA against survivin enhances the radiosensitivity of human non-small cell lung cancer cells. Cancer Gene Ther. (2009)
127. Hovelmann S., Beckers T.L., and Schmidt M. Molecular alterations in apoptotic pathways after PKB/Akt-mediated chemoresistance in NCI H460 cells. Br. J. Cancer 90 (2004) 2370-2377
128. Hayakawa J., Ohmichi M., Kurachi H., Kanda Y., Hisamoto K., Nishio Y., Adachi K., Tasaka K., Kanzaki T., and Murata Y. Inhibition of BAD phosphorylation either at serine 112 via extracellular signal-regulated protein kinase cascade or at serine 136 via Akt cascade sensitizes human ovarian cancer cells to cisplatin. Cancer Res. 60 (2000) 5988-5994
129. Page C., Lin H.J., Jin Y., Castle V.P., Nunez G., Huang M., and Lin J. Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis. Anticancer Res. 20 (2000) 407-416
130. Nelson J.M., and Fry D.W. Akt, MAPK (Erk1/2), and p38 act in concert to promote apoptosis in response to ErbB receptor family inhibition. J. Biol. Chem. 276 (2001) 14842-14847
131. Cheng J.Q., Jiang X., Fraser M., Li M., Dan H.C., Sun M., and Tsang B.K. Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian cancer: possible involvement of the phosphoinositide-3 kinase/Akt pathway. Drug Resist. Updat. 5 (2002) 131-146
132. Gagnon V., Mathieu I., Sexton E., Leblanc K., and Asselin E. AKT involvement in cisplatin chemoresistance of human uterine cancer cells. Gynecol. Oncol. 94 (2004) 785-795
133. Belyanskaya L.L., Hopkins-Donaldson S., Kurtz S., Simoes-Wust A.P., Yousefi S., Simon H.U., Stahel R., and Zangemeister-Wittke U. Cisplatin activates Akt in small cell lung cancer cells and attenuates apoptosis by survivin upregulation. Int. J. Cancer 117 (2005) 755-763
134. Kim D., Dan H.C., Park S., Yang L., Liu Q., Kaneko S., Ning J., He L., Yang H., Sun M., Nicosia S.V., and Cheng J.Q. AKT/PKB signaling mechanisms in cancer and chemoresistance. Front. Biosci. 10 (2005) 975-987
135. Tokunaga E., Kimura Y., Oki E., Ueda N., Futatsugi M., Mashino K., Yamamoto M., Ikebe M., Kakeji Y., Baba H., and Maehara Y. Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients. Int. J. Cancer 118 (2006) 284-289
136. Liu L.Z., Zhou X.D., Qian G., Shi X., Fang J., and Jiang B.H. AKT1 amplification regulates cisplatin resistance in human lung cancer cells through the mammalian target of rapamycin/p70S6K1 pathway. Cancer Res. 67 (2007) 6325-6332
137. Tamburini J., Elie C., Bardet V., Chapuis N., Park S., Broet P., Cornillet-Lefebvre P., Lioure B., Ugo V., Blanchet O., Ifrah N., Witz F., Dreyfus F., Mayeux P., Lacombe C., and Bouscary D. Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients. Blood 110 (2007) 1025-1028
138. Huang W.C., and Hung M.C. Induction of Akt activity by chemotherapy confers acquired resistance. J. Formos. Med. Assoc. 108 (2009) 180-194
139. Abedini M.R., Muller E.J., Bergeron R., Gray D.A., and Tsang B.K. Akt promotes chemoresistance in human ovarian cancer cells by modulating cisplatin-induced, p53-dependent ubiquitination of FLICE-like inhibitory protein. Oncogene 29 (2010) 11-25
140. Sizemore N., Leung S., and Stark G.R. Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to phosphorylation and activation of the NF-kappaB p65/RelA subunit. Mol. Cell. Biol. 19 (1999) 4798-4805
141. Kane L.P., Shapiro V.S., Stokoe D., and Weiss A. Induction of NF-kappaB by the Akt/PKB kinase. Curr. Biol. 9 (1999) 601-604
142. Meng F., Liu L., Chin P.C., and D'Mello S.R. Akt is a downstream target of NF-kappa B. J. Biol. Chem. 277 (2002) 29674-29680
143. Ng S.S., Tsao M.S., Nicklee T., and Hedley D.W. Wortmannin inhibits pkb/akt phosphorylation and promotes gemcitabine antitumor activity in orthotopic human pancreatic cancer xenografts in immunodeficient mice. Clin. Cancer Res. 7 (2001) 3269-3275
144. Tokunaga E., Kimura Y., Mashino K., Oki E., Kataoka A., Ohno S., Morita M., Kakeji Y., Baba H., and Maehara Y. Activation of PI3K/Akt signaling and hormone resistance in breast cancer. Breast Cancer 13 (2006) 137-144
145. Javle M.M., Yu J., Khoury T., Chadha K.S., Iyer R.V., Foster J., Kuvshinoff B.W., Gibbs J.F., Geradts J., Black J.D., and Brattain M.G. Akt expression may predict favorable prognosis in cholangiocarcinoma. J. Gastroenterol. Hepatol. 21 (2006) 1744-1751
146. Cataldi A., Zauli G., Di Pietro R., Castorina S., and Rana R. Involvement of the pathway phosphatidylinositol-3-kinase/AKT-1 in the establishment of the survival response to ionizing radiation. Cell. Signal. 13 (2001) 369-375
147. Gupta A.K., Cerniglia G.J., Mick R., Ahmed M.S., Bakanauskas V.J., Muschel R.J., and McKenna W.G. Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. Int. J. Radiat. Oncol. Biol. Phys. 56 (2003) 846-853
148. Tanno S., Yanagawa N., Habiro A., Koizumi K., Nakano Y., Osanai M., Mizukami Y., Okumura T., Testa J.R., and Kohgo Y. Serine/threonine kinase AKT is frequently activated in human bile duct cancer and is associated with increased radioresistance. Cancer Res. 64 (2004) 3486-3490
149. Soderlund K., Perez-Tenorio G., and Stal O. Activation of the phosphatidylinositol 3-kinase/Akt pathway prevents radiation-induced apoptosis in breast cancer cells. Int. J. Oncol. 26 (2005) 25-32
150. Kim T.J., Lee J.W., Song S.Y., Choi J.J., Choi C.H., Kim B.G., Lee J.H., and Bae D.S. Increased expression of pAKT is associated with radiation resistance in cervical cancer. Br. J. Cancer 94 (2006) 1678-1682
151. Kao G.D., Jiang Z., Fernandes A.M., Gupta A.K., and Maity A. Inhibition of phosphatidylinositol-3-OH kinase/Akt signaling impairs DNA repair in glioblastoma cells following ionizing radiation. J. Biol. Chem. 282 (2007) 21206-21212
152. Bussink J., van der Kogel A.J., and Kaanders J.H. Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. Lancet Oncol. 9 (2008) 288-296
153. Li H.F., Kim J.S., and Waldman T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat. Oncol. 4 (2009) 43
154. Liang K., Jin W., Knuefermann C., Schmidt M., Mills G.B., Ang K.K., Milas L., and Fan Z. Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy. Mol. Cancer Ther. 2 (2003) 353-360
155. Fujiwara K., Iwado E., Mills G.B., Sawaya R., Kondo S., and Kondo Y. Akt inhibitor shows anticancer and radiosensitizing effects in malignant glioma cells by inducing autophagy. Int. J. Oncol. 31 (2007) 753-760
156. Schmidt M., and Lichtner R.B. EGF receptor targeting in therapy-resistant human tumors. Drug Resist. Updat. 5 (2002) 11-18
157. Mendelsohn J., and Baselga J. Epidermal growth factor receptor targeting in cancer. Semin. Oncol. 33 (2006) 369-385
158. Garcia de Palazzo I.E., Adams G.P., Sundareshan P., Wong A.J., Testa J.R., Bigner D.D., and Weiner L.M. Expression of mutated epidermal growth factor receptor by non-small cell lung carcinomas. Cancer Res. 53 (1993) 3217-3220
159. Learn C.A., Hartzell T.L., Wikstrand C.J., Archer G.E., Rich J.N., Friedman A.H., Friedman H.S., Bigner D.D., and Sampson J.H. Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme. Clin. Cancer Res. 10 (2004) 3216-3224
160. Li B., Yuan M., Kim I.A., Chang C.M., Bernhard E.J., and Shu H.K. Mutant epidermal growth factor receptor displays increased signaling through the phosphatidylinositol-3 kinase/AKT pathway and promotes radioresistance in cells of astrocytic origin. Oncogene 23 (2004) 4594-4602
161. Nagane M., Levitzki A., Gazit A., Cavenee W.K., and Huang H.J. Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 5724-5729
162. Chen X., Yeung T.K., and Wang Z. Enhanced drug resistance in cells coexpressing ErbB2 with EGF receptor or ErbB3. Biochem. Biophys. Res. Commun. 277 (2000) 757-763
163. Hill C.S., and Treisman R. Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell 80 (1995) 199-211
164. Naruse I., Ohmori T., Ao Y., Fukumoto H., Kuroki T., Mori M., Saijo N., and Nishio K. Antitumor activity of the selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) Iressa (ZD1839) in an EGFR-expressing multidrug-resistant cell line in vitro and in vivo. Int. J. Cancer 98 (2002) 310-315
165. Dai Q., Ling Y.H., Lia M., Zou Y.Y., Kroog G., Iwata K.K., and Perez-Soler R. Enhanced sensitivity to the HER1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib hydrochloride in chemotherapy-resistant tumor cell lines. Clin. Cancer Res. 11 (2005) 1572-1578
166. Servidei T., Riccardi A., Mozzetti S., Ferlini C., and Riccardi R. Chemoresistant tumor cell lines display altered epidermal growth factor receptor and HER3 signaling and enhanced sensitivity to gefitinib. Int. J. Cancer 123 (2008) 2939-2949
167. Chen A.P., Zhang J., Liu H., Zhao S.P., Dai S.Z., and Sun X.L. Association of EGFR expression with angiogenesis and chemoresistance in ovarian carcinoma. Zhonghua Zhongliu Zazhi 31 (2009) 48-52
168. Kuroda H., Takeno M., Murakami S., Miyazawa N., Kaneko T., and Ishigatsubo Y. Inhibition of heme oxygenase-1 with an epidermal growth factor receptor inhibitor and cisplatin decreases proliferation of lung cancer A549 cells. Lung Cancer 67 (2010) 31-36
169. Akimoto T., Hunter N.R., Buchmiller L., Mason K., Ang K.K., and Milas L. Inverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas. Clin. Cancer Res. 5 (1999) 2884-2890
170. Liang K., Ang K.K., Milas L., Hunter N., and Fan Z. The epidermal growth factor receptor mediates radioresistance. Int. J. Radiat. Oncol. Biol. Phys. 57 (2003) 246-254
171. Milas L., Fan Z., Andratschke N.H., and Ang K.K. Epidermal growth factor receptor and tumor response to radiation: in vivo preclinical studies. Int. J. Radiat. Oncol. Biol. Phys. 58 (2004) 966-971
172. Toulany M., Dittmann K., Kruger M., Baumann M., and Rodemann H.P. Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway. Radiother. Oncol. 76 (2005) 143-150
173. Sarkaria J.N., Carlson B.L., Schroeder M.A., Grogan P., Brown P.D., Giannini C., Ballman K.V., Kitange G.J., Guha A., Pandita A., and James C.D. Use of an orthotopic xenograft model for assessing the effect of epidermal growth factor receptor amplification on glioblastoma radiation response. Clin. Cancer Res. 12 (2006) 2264-2271
174. Colquhoun A.J., McHugh L.A., Tulchinsky E., Kriajevska M., and Mellon J.K. Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo. J. Radiat. Res. (Tokyo) 48 (2007) 351-360
175. Geoerger B., Gaspar N., Opolon P., Morizet J., Devanz P., Lecluse Y., Valent A., Lacroix L., Grill J., and Vassal G. EGFR tyrosine kinase inhibition radiosensitizes and induces apoptosis in malignant glioma and childhood ependymoma xenografts. Int. J. Cancer 123 (2008) 209-216
176. Jing Z., Gong L., Xie C.Y., Zhang L., Su H.F., Deng X., and Wu S.X. Reverse resistance to radiation in KYSE-150R esophageal carcinoma cell after epidermal growth factor receptor signal pathway inhibition by cetuximab. Radiother. Oncol. 93 (2009) 468-473
177. Ping Y., Jian Z., Yi Z., Huoyu Z., Feng L., Yuqiong Y., and Shixi L. Inhibition of the EGFR with nanoparticles encapsulating antisense oligonucleotides of the EGFR enhances radiosensitivity in SCCVII cells. Med. Oncol. (2009)
178. Wang C.Y., Cusack Jr. J.C., Liu R., and Baldwin Jr. A.S. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat. Med. 5 (1999) 412-417
179. Patel N.M., Nozaki S., Shortle N.H., Bhat-Nakshatri P., Newton T.R., Rice S., Gelfanov V., Boswell S.H., Goulet Jr. R.J., Sledge Jr. G.W., and Nakshatri H. Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide. Oncogene 19 (2000) 4159-4169
180. Jones D.R., Broad R.M., Madrid L.V., Baldwin Jr. A.S., and Mayo M.W. Inhibition of NF-kappaB sensitizes non-small cell lung cancer cells to chemotherapy-induced apoptosis. Ann. Thorac. Surg. 70 (2000) 930-936 discussion 936-937.
181. Arlt A., Vorndamm J., Breitenbroich M., Folsch U.R., Kalthoff H., Schmidt W.E., and Schafer H. Inhibition of NF-kappaB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin. Oncogene 20 (2001) 859-868
182. Cusack Jr. J.C., Liu R., Houston M., Abendroth K., Elliott P.J., Adams J., and Baldwin Jr. A.S. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res. 61 (2001) 3535-3540
183. Chuang S.E., Yeh P.Y., Lu Y.S., Lai G.M., Liao C.M., Gao M., and Cheng A.L. Basal levels and patterns of anticancer drug-induced activation of nuclear factor-kappaB (NF-kappaB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells. Biochem. Pharmacol. 63 (2002) 1709-1716
184. Flynn Jr. V., Ramanitharan A., Moparty K., Davis R., Sikka S., Agrawal K.C., and Abdel-Mageed A.B. Adenovirus-mediated inhibition of NF-kappaB confers chemo-sensitization and apoptosis in prostate cancer cells. Int. J. Oncol. 23 (2003) 317-323
185. Muerkoster S., Arlt A., Witt M., Gehrz A., Haye S., March C., Grohmann F., Wegehenkel K., Kalthoff H., Folsch U.R., and Schafer H. Usage of the NF-kappaB inhibitor sulfasalazine as sensitizing agent in combined chemotherapy of pancreatic cancer. Int. J. Cancer 104 (2003) 469-476
186. Guo J., Verma U.N., Gaynor R.B., Frenkel E.P., and Becerra C.R. Enhanced chemosensitivity to irinotecan by RNA interference-mediated down-regulation of the nuclear factor-kappaB p65 subunit. Clin. Cancer Res. 10 (2004) 3333-3341
187. Mabuchi S., Ohmichi M., Nishio Y., Hayasaka T., Kimura A., Ohta T., Saito M., Kawagoe J., Takahashi K., Yada-Hashimoto N., Sakata M., Motoyama T., Kurachi H., Tasaka K., and Murata Y. Inhibition of NFkappaB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models. J. Biol. Chem. 279 (2004) 23477-23485
188. Banerjee S., Zhang Y., Ali S., Bhuiyan M., Wang Z., Chiao P.J., Philip P.A., Abbruzzese J., and Sarkar F.H. Molecular evidence for increased antitumor activity of gemcitabine by genistein in vitro and in vivo using an orthotopic model of pancreatic cancer. Cancer Res. 65 (2005) 9064-9072
189. Salvatore C., Camarda G., Maggi C.A., Goso C., Manzini S., and Binaschi M. NF-kappaB activation contributes to anthracycline resistance pathway in human ovarian carcinoma cell line A2780. Int. J. Oncol. 27 (2005) 799-806
190. Kwon O., Kim K.A., Kim S.O., Ha R., Oh W.K., Kim M.S., Kim H.S., Kim G.D., Kim J.W., Jung M., Kim C.H., Ahn J.S., and Kim B.Y. NF-kappaB inhibition increases chemosensitivity to trichostatin A-induced cell death of Ki-Ras-transformed human prostate epithelial cells. Carcinogenesis 27 (2006) 2258-2268
191. Kim D.S., Park S.S., Nam B.H., Kim I.H., and Kim S.Y. Reversal of drug resistance in breast cancer cells by transglutaminase 2 inhibition and nuclear factor-kappaB inactivation. Cancer Res. 66 (2006) 10936-10943
192. Sun C., Chan F., Briassouli P., and Linardopoulos S. Aurora kinase inhibition downregulates NF-kappaB and sensitises tumour cells to chemotherapeutic agents. Biochem. Biophys. Res. Commun. 352 (2007) 220-225
193. Kunnumakkara A.B., Guha S., Krishnan S., Diagaradjane P., Gelovani J., and Aggarwal B.B. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 67 (2007) 3853-3861
194. Tapia M.A., Gonzalez-Navarrete I., Dalmases A., Bosch M., Rodriguez-Fanjul V., Rolfe M., Ross J.S., Mezquita J., Mezquita C., Bachs O., Gascon P., Rojo F., Perona R., Rovira A., and Albanell J. Inhibition of the canonical IKK/NF kappa B pathway sensitizes human cancer cells to doxorubicin. Cell Cycle 6 (2007) 2284-2292
195. Schon M., Wienrich B.G., Kneitz S., Sennefelder H., Amschler K., Vohringer V., Weber O., Stiewe T., Ziegelbauer K., and Schon M.P. KINK-1, a novel small-molecule inhibitor of IKKbeta, and the susceptibility of melanoma cells to antitumoral treatment. J. Natl. Cancer Inst. 100 (2008) 862-875
196. Mi J., Zhang X., Rabbani Z.N., Liu Y., Reddy S.K., Su Z., Salahuddin F.K., Viles K., Giangrande P.H., Dewhirst M.W., Sullenger B.A., Kontos C.D., and Clary B.M. RNA aptamer-targeted inhibition of NF-kappa B suppresses non-small cell lung cancer resistance to doxorubicin. Mol. Ther. 16 (2008) 66-73
197. Sors A., Jean-Louis F., Begue E., Parmentier L., Dubertret L., Dreano M., Courtois G., Bachelez H., and Michel L. Inhibition of IkappaB kinase subunit 2 in cutaneous T-cell lymphoma down-regulates nuclear factor-kappaB constitutive activation, induces cell death, and potentiates the apoptotic response to antineoplastic chemotherapeutic agents. Clin. Cancer Res. 14 (2008) 901-911
198. Sung B., Kunnumakkara A.B., Sethi G., Anand P., Guha S., and Aggarwal B.B. Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model. Mol. Cancer Ther. 8 (2009) 959-970
199. Kunnumakkara A.B., Diagaradjane P., Anand P., Kuzhuvelil H.B., Deorukhkar A., Gelovani J., Guha S., Krishnan S., and Aggarwal B.B. Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic mouse model. Int. J. Cancer 125 (2009) 2187-2197
200. Bold R.J., Virudachalam S., and McConkey D.J. Chemosensitization of pancreatic cancer by inhibition of the 26S proteasome. J. Surg. Res. 100 (2001) 11-17
201. Murtaza I., Adhami V.M., Hafeez B.B., Saleem M., and Mukhtar H. Fisetin, a natural flavonoid, targets chemoresistant human pancreatic cancer AsPC-1 cells through DR3-mediated inhibition of NF-kappaB. Int. J. Cancer 125 (2009) 2465-2473
202. Shao R., Karunagaran D., Zhou B.P., Li K., Lo S.S., Deng J., Chiao P., and Hung M.C. Inhibition of nuclear factor-kappaB activity is involved in E1A-mediated sensitization of radiation-induced apoptosis. J. Biol. Chem. 272 (1997) 32739-32742
203. Yamagishi N., Miyakoshi J., and Takebe H. Enhanced radiosensitivity by inhibition of nuclear factor kappa B activation in human malignant glioma cells. Int. J. Radiat. Biol. 72 (1997) 157-162
204. Bradbury C.M., Markovina S., Wei S.J., Rene L.M., Zoberi I., Horikoshi N., and Gius D. Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase. Cancer Res. 61 (2001) 7689-7696
205. Didelot C., Barberi-Heyob M., Bianchi A., Becuwe P., Mirjolet J.F., Dauca M., and Merlin J.L. Constitutive NF-kappaB activity influences basal apoptosis and radiosensitivity of head-and-neck carcinoma cell lines. Int. J. Radiat. Oncol. Biol. Phys. 51 (2001) 1354-1360
206. Russo S.M., Tepper J.E., Baldwin Jr. A.S., Liu R., Adams J., Elliott P., and Cusack Jr. J.C. Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB. Int. J. Radiat. Oncol. Biol. Phys. 50 (2001) 183-193
207. Raju U., Nakata E., Yang P., Newman R.A., Ang K.K., and Milas L. In vitro enhancement of tumor cell radiosensitivity by a selective inhibitor of cyclooxygenase-2 enzyme: mechanistic considerations. Int. J. Radiat. Oncol. Biol. Phys. 54 (2002) 886-894
208. Kim K.M., Zhang Y., Kim B.Y., Jeong S.J., Lee S.A., Kim G.D., Dritschilo A., and Jung M. The p65 subunit of nuclear factor-kappaB is a molecular target for radiation sensitization of human squamous carcinoma cells. Mol. Cancer Ther. 3 (2004) 693-698
209. Munshi A., Kurland J.F., Nishikawa T., Chiao P.J., Andreeff M., and Meyn R.E. Inhibition of constitutively activated nuclear factor-kappaB radiosensitizes human melanoma cells. Mol. Cancer Ther. 3 (2004) 985-992
210. Kim B.Y., Kim K.A., Kwon O., Kim S.O., Kim M.S., Kim B.S., Oh W.K., Kim G.D., Jung M., and Ahn J.S. NF-kappaB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation. Carcinogenesis 26 (2005) 1395-1403
211. Crokart N., Radermacher K., Jordan B.F., Baudelet C., Cron G.O., Gregoire V., Beghein N., Bouzin C., Feron O., and Gallez B. Tumor radiosensitization by antiinflammatory drugs: evidence for a new mechanism involving the oxygen effect. Cancer Res. 65 (2005) 7911-7916
212. Kim I.A., Bae S.S., Fernandes A., Wu J., Muschel R.J., McKenna W.G., Birnbaum M.J., and Bernhard E.J. Selective inhibition of Ras, phosphoinositide 3 kinase, and Akt isoforms increases the radiosensitivity of human carcinoma cell lines. Cancer Res. 65 (2005) 7902-7910
213. Choi C.H., Xu H., Bark H., Lee T.B., Yun J., Kang S.I., and Oh Y.K. Balance of NF-kappaB and p38 MAPK is a determinant of radiosensitivity of the AML-2 and its doxorubicin-resistant cell lines. Leuk. Res. 31 (2007) 1267-1276
214. Voboril R., and Weberova-Voborilova J. Sensitization of colorectal cancer cells to irradiation by IL-4 and IL-10 is associated with inhibition of NF-kappaB. Neoplasma 54 (2007) 495-502
215. Zand H., Rahimipour A., Salimi S., and Shafiee S.M. Docosahexaenoic acid sensitizes Ramos cells to Gamma-irradiation-induced apoptosis through involvement of PPAR-gamma activation and NF-kappaB suppression. Mol. Cell. Biochem. 317 (2008) 113-120
216. Aravindan N., Madhusoodhanan R., Ahmad S., Johnson D., and Herman T.S. Curcumin inhibits NFkappaB mediated radioprotection and modulate apoptosis related genes in human neuroblastoma cells. Cancer Biol. Ther. 7 (2008) 569-576
217. Kunnumakkara A.B., Diagaradjane P., Guha S., Deorukhkar A., Shentu S., Aggarwal B.B., and Krishnan S. Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappaB-regulated gene products. Clin. Cancer Res. 14 (2008) 2128-2136
218. Sandur S.K., Deorukhkar A., Pandey M.K., Pabon A.M., Shentu S., Guha S., Aggarwal B.B., and Krishnan S. Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity. Int. J. Radiat. Oncol. Biol. Phys. 75 (2009) 534-542
219. Tsuboi Y., Kurimoto M., Nagai S., Hayakawa Y., Kamiyama H., Hayashi N., Kitajima I., and Endo S. Induction of autophagic cell death and radiosensitization by the pharmacological inhibition of nuclear factor-kappa B activation in human glioma cell lines. J. Neurosurg. 110 (2009) 594-604
220. Pajonk F., and McBride W.H. Ionizing radiation affects 26S proteasome function and associated molecular responses, even at low doses. Radiother. Oncol. 59 (2001) 203-212
221. Pajonk F., Pajonk K., and McBride W.H. Inhibition of NF-kappaB, clonogenicity, and radiosensitivity of human cancer cells. J. Natl. Cancer Inst. 91 (1999) 1956-1960
222. Garg A.K., Buchholz T.A., and Aggarwal B.B. Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid. Redox Signal. 7 (2005) 1630-1647
223. Koki A.T., Leahy K.M., and Masferrer J.L. Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy. Expert Opin. Investig. Drugs 8 (1999) 1623-1638
224. Hideshima T., Chauhan D., Richardson P., Mitsiades C., Mitsiades N., Hayashi T., Munshi N., Dang L., Castro A., Palombella V., Adams J., and Anderson K.C. NF-kappa B as a therapeutic target in multiple myeloma. J. Biol. Chem. 277 (2002) 16639-16647
225. Denlinger C.E., Rundall B.K., Keller M.D., and Jones D.R. Proteasome inhibition sensitizes non-small-cell lung cancer to gemcitabine-induced apoptosis. Ann. Thorac. Surg. 78 (2004) 1207-1214 discussion 1207-1214.
226. Scaife C.L., Kuang J., Wills J.C., Trowbridge D.B., Gray P., Manning B.M., Eichwald E.J., Daynes R.A., and Kuwada S.K. Nuclear factor kappaB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis. Cancer Res. 62 (2002) 6870-6878
227. Yamamoto Y., Yin M.J., Lin K.M., and Gaynor R.B. Sulindac inhibits activation of the NF-kappaB pathway. J. Biol. Chem. 274 (1999) 27307-27314
228. Yin M.J., Yamamoto Y., and Gaynor R.B. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 396 (1998) 77-80
229. Fulda S., and Debatin K.M. Sensitization for anticancer drug-induced apoptosis by the chemopreventive agent resveratrol. Oncogene 23 (2004) 6702-6711
230. Li Y., Ahmed F., Ali S., Philip P.A., Kucuk O., and Sarkar F.H. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res. 65 (2005) 6934-6942
231. Zhang L., Lau Y.K., Xia W., Hortobagyi G.N., and Hung M.C. Tyrosine kinase inhibitor emodin suppresses growth of HER-2/neu-overexpressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel. Clin. Cancer Res. 5 (1999) 343-353
232. Zhou L., Liu P., Chen B., Wang Y., Wang X., Internati M.C., Wachtel M.S., and Frezza E.E. Silibinin restores paclitaxel sensitivity to paclitaxel-resistant human ovarian carcinoma cells. Anticancer Res. 28 (2008) 1119-1127
233. Sadzuka Y., Sugiyama T., and Sonobe T. Efficacies of tea components on doxorubicin induced antitumor activity and reversal of multidrug resistance. Toxicol. Lett. 114 (2000) 155-162
234. Gomez L.A., de Las Pozas A., and Perez-Stable C. Sequential combination of flavopiridol and docetaxel reduces the levels of X-linked inhibitor of apoptosis and AKT proteins and stimulates apoptosis in human LNCaP prostate cancer cells. Mol. Cancer Ther. 5 (2006) 1216-1226
235. Zoberi I., Bradbury C.M., Curry H.A., Bisht K.S., Goswami P.C., Roti Roti J.L., and Gius D. Radiosensitizing and anti-proliferative effects of resveratrol in two human cervical tumor cell lines. Cancer Lett. 175 (2002) 165-173
236. Akimoto T., Nonaka T., Ishikawa H., Sakurai H., Saitoh J.I., Takahashi T., and Mitsuhashi N. Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro: possible involvement of inhibition of survival signal transduction pathways. Int. J. Radiat. Oncol. Biol. Phys. 50 (2001) 195-201
237. Komatsu K., Tauchi H., Yano N., Endo S., Matsuura S., and Shoji S. Inhibitory action of (-)-epigallocatechin gallate on radiation-induced mouse oncogenic transformation. Cancer Lett. 112 (1997) 135-139
238. Raju U., Nakata E., Mason K.A., Ang K.K., and Milas L. Flavopiridol, a cyclin-dependent kinase inhibitor, enhances radiosensitivity of ovarian carcinoma cells. Cancer Res. 63 (2003) 3263-3267
239. Nasu S., Milas L., Kawabe S., Raju U., and Newman R. Enhancement of radiotherapy by oleandrin is a caspase-3 dependent process. Cancer Lett. 185 (2002) 145-151
240. Sharada A.C., Solomon F.E., Devi P.U., Udupa N., and Srinivasan K.K. Antitumor and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma in vivo. Acta Oncol. 35 (1996) 95-100
241. Devi P.U., Rao B.S., and Solomon F.E. Effect of plumbagin on the radiation induced cytogenetic and cell cycle changes in mouse Ehrlich ascites carcinoma in vivo. Indian J. Exp. Biol. 36 (1998) 891-895