Molecular impacts of rapamycin-based drug combinations: Combining rapamycin with gemcitabine or imatinib mesylate (Gleevec) in a human leiomyosarcoma model

International Journal of Oncology

Volumn 31, Issue 1, 2007, Pages 225-232

  Merimsky, Ofer ^a   Gorzalczany, Yaara ^b   Sagi Eisenberg, Ronit ^b  

^a TEL AVIV SOURASKY MEDICAL CENTER   (Israel)

^b TEL AVIV UNIVERSITY   (Israel)

Author keywords

Gemcitabine; Imatinib mesylate (Gleevec); Leiomyosarcoma; Rapamycin; Signaling

Indexed keywords

ANTINEOPLASTIC AGENT; DEOXYCYTIDINE; DRUG DERIVATIVE; GEMCITABINE; IMATINIB; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PIPERAZINE DERIVATIVE; PYRIMIDINE DERIVATIVE; RAPAMYCIN;

ARTICLE; BIOLOGICAL MODEL; CELL CYCLE; CELL PROLIFERATION; DRUG EFFECT; HUMAN; LEIOMYOSARCOMA; METABOLISM; MITOCHONDRIAL MEMBRANE POTENTIAL; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; DEOXYCYTIDINE; HUMANS; LEIOMYOSARCOMA; MEMBRANE POTENTIAL, MITOCHONDRIAL; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MODELS, BIOLOGICAL; PIPERAZINES; PYRIMIDINES; SIGNAL TRANSDUCTION; SIROLIMUS;

EID: 34548555671     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.31.1.225     Document Type: Article

References (37)

1. Pommier Y, Sordet O, Antony S, Hayward RL and Kohn KW: Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene 23: 2934-2949, 2004.
2. Dupont P and Warrens AN: The evolving role of sirolimus in renal transplantation. QJM 96: 401-409, 2003.
3. Albert JM, Kim KW, Cao C and Lu B: Targeting the Akt/mammalian target of rapamycin pathway for radiosensitization of breast cancer. Mol Cancer Ther 5: 1183-1189, 2006.
4. Dancey JE: Inhibitors of the mammalian target of rapamycin. Expert Opin Investig Drugs 14: 313-328, 2005.
5. Keith CT and Schreiber SL: PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science 270: 50-51, 1995.
6. Dancey JE: Molecular targeting: PI3 kinase pathway. Ann Oncol 15: 233-239, 2004.
7. Kim D, Cheng G, Lindsley C, Yang H and Cheng J: Targeting the phosphatidylinositol-3 kinase/Akt pathway for the treatment of cancer. Curr Opin Investig Drugs 6: 1250-1258, 2005.
8. Hui YF and Reitz J: Gemcitabine: a cytidine analogue active against solid tumors. Am J Health Syst Pharm 54: 162-170, 1997.
9. Merimsky O, Meller I, Flusser G, et al: Gemcitabine in soft tissue or bone sarcoma resistant to standard chemotherapy: a phase II study. Cancer Chemother Pharmacol 45: 177-181, 2000.
10. Patel SR, Gandhi V, Jenkins J, et al: Phase II clinical investigation of gemcitabine in advanced soft tissue sarcomas and window evaluation of dose rate on gemcitabine triphosphate accumulation. J Clin Oncol 19: 3483-3489, 2001.
11. Arlt A, Gehrz A, Müerköster S, et al: Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene 22: 3243-3251, 2003.
12. Oguri T, Achiwa H, Sato S, et al: The determinants of sensitivity and acquired resistance to gemcitabine differ in non-small cell lung cancer: a role of ABCC5 in gemcitabine sensitivity. Mol Cancer Ther 5: 1800-1806, 2006.
13. Williams J, Lucas PC, Griffith KA, et al: Expression of Bcl-xL in ovarian carcinoma is associated with chemoresistance and recurrent disease. Gynecol Oncol 96: 287-295, 2005.
14. Merimsky O: Targeting metastatic leiomyosarcoma by rapamycin plus gemcitabine: an intriguing clinical observation. Int J Mol Med 14: 931-935, 2004.
15. Loizos N, Xu Y, Huber J, et al: Targeting the platelet-derived growth factor receptor {alpha} with a neutralizing human monoclonal antibody inhibits the growth of tumor xenografts: Implications as a potential therapeutic target. Mol Cancer Ther 4: 369-379, 2005.
16. Heinrich MC, Griffith DJ, Druker BJ, Wait CL, Ott KA and Zigler AJ: Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96: 925-932, 2000.
17. Buchdunger E, Cioffi CL, Law N, et al: Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-Kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 295: 139-145, 2000.
18. Salvioli S, Ardizzoni A, Franceschi C and Cossarizza A: JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess [Delta][Psi] changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Letters 411: 77-82, 1997.
19. Brown EJ, Albers MW, Shin TB, et al: A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 369: 756-758, 1994.
20. Green DR and Reed JC: Mitochondria and apoptosis. Science 281: 1309-1312, 1998.
21. Ly JD, Grubb DR and Lawen A: The mitochondrial membrane potential in apoptosis; an update. Apoptosis 8: 115-128, 2003.
22. Kroemer G, Dallaporta B and Resche-Rigon M: The mitochondrial death/life regulator in apoptosis and necrosis. Ann Rev Physiol 60: 619-642, 1998. (Pubitemid 28157889)
23. Cappuzzo F, Toschi L, Finocchiaro G, Bartolini S and Gioia V: Role of gemcitabine in cancer therapy. Future Oncol 1: 7-17, 2005.
24. Cappuzzo F and Crino L: Gemcitabine in non-small cell lung cancer. Expert Opin Pharmacother 3: 745-753, 2002.
25. Bauer S, Seeber S and Schutte J: Gemcitabine in the treatment of Soft Tissue Sarcomas. Onkologie 27: 180-186, 2004.
26. Chang G-C, Hsu S-L, Tsai J-R, Wu W-J, Chen C-Y and Sheu G-T: Extracellular signal-regulated kinase activation and Bcl-2 downregulation mediate apoptosis after gemcitabine treatment partly via a p53-independent pathway. Eur J Pharmacol 502: 169-183, 2004.
27. Yokoi K and Fidler IJ: Hypoxia increases resistance of human pancreatic cancer cells to apoptosis induced by gemcitabine. Clin Cancer Res 10: 2299-2306, 2004.
28. Kim D-H, Sarbassov DD, Ali SM, et al: mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110: 163-175, 2002.
29. Sarbassov DD, Ali SM, Sengupta S, et al: Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22: 159-168, 2006.
30. Yoeli-Lerner M, Yiu GK, Rabinovitz I, Erhardt P, Jauliac S and Toker A: Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT. Mol Cell 20: 539-550, 2005.
31. Stambolic V and Woodgett JR: Functional distinctions of protein kinase B/Akt isoforms defined by their influence on cell migration. Trends Cell Biol 16: 461-466, 2006.
32. Okuno S: Mammalian target of rapamycin inhibitors in sarcomas. Sarcomas. Curr Opin Oncol 18: 360-362, 2006.
33. Bruns CJ, Koehl GE, Guba M, et al: Rapamycin-induced endothelial cell death and tumor vessel thrombosis potentiate cytotoxic therapy against pancreatic cancer. Clin Cancer Res 10: 2109-2119, 2004.
34. Mohi MG, Boulton C, Gu T-L, et al: Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs. PNAS 101: 3130-3135, 2004.
35. Feng FY, Varambally S, Tomlins SA, et al: Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity. Oncogene 2006 (Epub ahead of print).
36. Paglin S, Lee N-Y, Nakar C, et al: Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells. Cancer Res 65: 11061-11070, 2005.
37. Khaled AR, Reynolds DA, Young HA, Thompson CB, Muegge K and Durum SK: Interleukin-3 withdrawal induces an early increase in mitochondrial membrane potential unrelated to the Bcl-2 family. Roles of intracellular pH, ADP transport, and F0F1-ATPase. J Biol Chem 276: 6453-6462, 2001.