The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

Biochemical and Biophysical Research Communications

Volumn 450, Issue 2, 2014, Pages 973-978

  Lou, Hai Zhou ^a   Weng, Xiao Chuan ^b   Pan, Hong Ming ^a   Pan, Qin ^a   Sun, Peng ^c   Liu, Li Li ^a   Chen, Bin ^d  

^a ZHEJIANG UNIVERSITY   (China)

^b Hangzhou Xiasha Hospital   (China)

^c SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^d HANGZHOU FIRST PEOPLE'S HOSPITAL   (China)

Author keywords

Akt mTOR signaling; Apoptosis and gemcitabine sensitization; INK 128; Pancreatic cancer

Indexed keywords

ANTINEOPLASTIC AGENT; CYCLIN D1; GEMCITABINE; INITIATION FACTOR 4E BINDING PROTEIN 1; INK 128; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PROTEIN KINASE B; RIBOSOMAL S6 KINASE 1; S6 KINASE; SERINE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CANCER CELL; CELL CYCLE ARREST; CELL DEATH; CELL GROWTH; CELL PROLIFERATION; CELL SURVIVAL; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG CYTOTOXICITY; DRUG SENSITIZATION; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IN VITRO STUDY; PANCREAS CANCER; PRIMARY CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; TRANSFORMED CELL;

AKT/MTOR SIGNALING; APOPTOSIS AND GEMCITABINE SENSITIZATION; INK-128; PANCREATIC CANCER;

ADENOCARCINOMA; ADULT; ANTINEOPLASTIC AGENTS; APOPTOSIS; BENZOXAZOLES; CELL LINE, TRANSFORMED; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; DEOXYCYTIDINE; DRUG SYNERGISM; HUMANS; MALE; MULTIPROTEIN COMPLEXES; NECROSIS; PANCREATIC NEOPLASMS; PYRIMIDINES; TOR SERINE-THREONINE KINASES;

EID: 84905119809     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2014.06.081     Document Type: Article

References (38)

1. R. Siegel, J. Ma, Z. Zou, and A. Jemal Cancer statistics CA Cancer J. Clin. 64 2014 2014 9 29
2. E. Costello, and J.P. Neoptolemos Pancreatic cancer in 2010: new insights for early intervention and detection Nat. Rev. Gastroenterol. Hepatol. 8 2011 71 73
3. M. Ducreux, V. Boige, and D. Malka Treatment of advanced pancreatic cancer Semin. Oncol. 34 2007 S25 S30
4. M. Hidalgo Pancreatic cancer N. Engl. J. Med. 362 2010 1605 1617
5. H.Q. Xiong, K. Carr, and J.L. Abbruzzese Cytotoxic chemotherapy for pancreatic cancer: advances to date and future directions Drugs 66 2006 1059 1072 (Pubitemid 43945867)
6. D.A. Fruman, and C. Rommel PI3K and cancer: lessons, challenges and opportunities Nat. Rev. Drug Discov. 13 2014 140 156
7. B.T. Hennessy, D.L. Smith, P.T. Ram, Y. Lu, and G.B. Mills Exploiting the PI3K/AKT pathway for cancer drug discovery Nat. Rev. Drug Discov. 4 2005 988 1004
8. J. Rodon, R. Dienstmann, V. Serra, and J. Tabernero Development of PI3K inhibitors: lessons learned from early clinical trials Nat. Rev. Clin. Oncol. 10 2013 143 153
9. B. Vanhaesebroeck, L. Stephens, and P. Hawkins PI3K signalling: the path to discovery and understanding Nat. Rev. Mol. Cell. Biol. 13 2012 195 203
10. M. Falasca, F. Selvaggi, R. Buus, S. Sulpizio, and C.E. Edling Targeting phosphoinositide 3-kinase pathways in pancreatic cancer - from molecular signalling to clinical trials Anticancer Agents Med. Chem. 11 2011 455 463
11. T. Furukawa Molecular targeting therapy for pancreatic cancer: current knowledge and perspectives from bench to bedside J. Gastroenterol. 43 2008 905 911
12. A. Efeyan, and D.M. Sabatini mTOR and cancer: many loops in one pathway Curr. Opin. Cell Biol. 22 2010 169 176
13. D.A. Guertin, and D.M. Sabatini Defining the role of mTOR in cancer Cancer Cell 12 2007 9 22 (Pubitemid 47001784)
14. M. Laplante, and D.M. Sabatini mTOR signaling in growth control and disease Cell 149 2012 274 293
15. D.M. Sabatini mTOR and cancer: insights into a complex relationship Nat. Rev. Cancer 6 2006 729 734 (Pubitemid 44286004)
16. M. Shimobayashi, and M.N. Hall Making new contacts: the mTOR network in metabolism and signalling crosstalk Nat. Rev. Mol. Cell. Biol. 15 2014 155 162
17. S.Y. Sun mTOR kinase inhibitors as potential cancer therapeutic drugs Cancer Lett. 340 2013 1 8
18. A. Gomez-Pinillos, and A.C. Ferrari mTOR signaling pathway and mTOR inhibitors in cancer therapy Hematol. Oncol. Clin. N. Am. 26 2012 483 505 (vii)
19. H.Y. Zhou, and S.L. Huang Current development of the second generation of mTOR inhibitors as anticancer agents Chin. J. Cancer 31 2012 8 18
20. Y.Y. Zaytseva, J.D. Valentino, P. Gulhati, and B.M. Evers mTOR inhibitors in cancer therapy Cancer Lett. 319 2012 1 7
21. C. Garcia-Echeverria Allosteric and ATP-competitive kinase inhibitors of mTOR for cancer treatment Bioorg. Med. Chem. Lett. 20 2010 4308 4312
22. C. Garcia-Garcia, Y.H. Ibrahim, V. Serra, M.T. Calvo, M. Guzman, J. Grueso, C. Aura, J. Perez, K. Jessen, Y. Liu, C. Rommel, J. Tabernero, J. Baselga, and M. Scaltriti Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy Clin. Cancer Res. 18 2012 2603 2612
23. H. Min, M. Xu, Z.R. Chen, J.D. Zhou, M. Huang, K. Zheng, and X.P. Zou Bortezomib induces protective autophagy through AMP-activated protein kinase activation in cultured pancreatic and colorectal cancer cells Cancer Chemother. Pharmacol. 74 2014 167 176
24. J.S. Kim, J.Y. Kang, J.H. Ha, H.Y. Lee, S.J. Kim, S.C. Kim, J.H. Ahn, S.S. Kwon, Y.K. Kim, and S.Y. Lee Expression of nerve growth factor and matrix metallopeptidase-9/tissue inhibitor of metalloproteinase-1 in asthmatic patients J. Asthma 50 2013 712 717
25. D.W. Chan, B.P. Chen, S. Prithivirajsingh, A. Kurimasa, M.D. Story, J. Qin, and D.J. Chen Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks Genes Dev. 16 2002 2333 2338 (Pubitemid 35034402)
26. C.A. Sparks, and D.A. Guertin Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy Oncogene 29 2010 3733 3744
27. J. Averous, B.D. Fonseca, and C.G. Proud Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1 Oncogene 27 2008 1106 1113 (Pubitemid 351253179)
28. C. Cao, X. Huang, Y. Han, Y. Wan, L. Birnbaumer, G.S. Feng, J. Marshall, M. Jiang, and W.M. Chu Galpha(i1) and Galpha(i3) are required for epidermal growth factor-mediated activation of the Akt-mTORC1 pathway Sci. Signal 2 2009 ra17
29. I. Garrido-Laguna, A.C. Tan, M. Uson, M. Angenendt, W.W. Ma, M.C. Villaroel, M. Zhao, N.V. Rajeshkumar, A. Jimeno, R. Donehower, C. Iacobuzio-Donahue, M. Barrett, M.A. Rudek, B. Rubio-Viqueira, D. Laheru, and M. Hidalgo Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer Br. J. Cancer 103 2010 649 655
30. D. Ito, K. Fujimoto, T. Mori, K. Kami, M. Koizumi, E. Toyoda, Y. Kawaguchi, and R. Doi In vivo antitumor effect of the mTOR inhibitor CCI-779 and gemcitabine in xenograft models of human pancreatic cancer Int. J. Cancer 118 2006 2337 2343
31. J. Dancey mTOR signaling and drug development in cancer Nat. Rev. Clin. Oncol. 7 2010 209 219
32. I.R. Konings, J. Verweij, E.A. Wiemer, and S. Sleijfer The applicability of mTOR inhibition in solid tumors Curr. Cancer Drug Targets 9 2009 439 450
33. E. Vilar, J. Perez-Garcia, and J. Tabernero Pushing the envelope in the mTOR pathway: the second generation of inhibitors Mol. Cancer Ther. 10 2011 395 403
34. K.E. O'Reilly, F. Rojo, Q.B. She, D. Solit, G.B. Mills, D. Smith, H. Lane, F. Hofmann, D.J. Hicklin, D.L. Ludwig, J. Baselga, and N. Rosen mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt Cancer Res. 66 2006 1500 1508 (Pubitemid 43259931)
35. X. Wan, B. Harkavy, N. Shen, P. Grohar, and L.J. Helman Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism Oncogene 26 2007 1932 1940 (Pubitemid 46474636)
36. A. Carracedo, L. Ma, J. Teruya-Feldstein, F. Rojo, L. Salmena, A. Alimonti, A. Egia, A.T. Sasaki, G. Thomas, S.C. Kozma, A. Papa, C. Nardella, L.C. Cantley, J. Baselga, and P.P. Pandolfi Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer J. Clin. Invest. 118 2008 3065 3074
37. V. Papadimitrakopoulou Development of PI3K/AKT/mTOR pathway inhibitors and their application in personalized therapy for non-small-cell lung cancer J. Thorac. Oncol. 7 2012 1315 1326
38. M.C. Lin, K.S. Rojas, R.A. Cerione, and K.F. Wilson Identification of mTORC2 as a necessary component of HRG/ErbB2-dependent cellular transformation Mol. Cancer Res. 12 2014 940 952