PKI-587 and sorafenib targeting PI3K/AKT/mTOR and Ras/Raf/MAPK pathways synergistically inhibit HCC cell proliferation

Journal of Surgical Research

Volumn 176, Issue 2, 2012, Pages 542-548

  Gedaly, Roberto ^a   Angulo, Paul ^a   Hundley, Jonathan ^a   Daily, Michael F ^a   Chen, Changguo ^a   Evers, B Mark ^a,b  

^a UNIVERSITY OF KENTUCKY   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

Author keywords

epidermal growth factor; mTOR complex 1; mTOR complex 2; negative feedback loop; PI 103; PKI 587; rapamycin; sorafenib

Indexed keywords

2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 3 (4,5 DIMETHYL 2 THIAZOLYL) 2,5 DIPHENYLTETRAZOLIUM BROMIDE; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHOTRANSFERASE; PKI 587; PROTEIN KINASE B; PROTEIN SERINE THREONINE KINASE; RAF PROTEIN; RAS PROTEIN; SORAFENIB; UNCLASSIFIED DRUG;

ARTICLE; CANCER INHIBITION; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; PRIORITY JOURNAL; PROTEIN TARGETING; SIGNAL TRANSDUCTION;

ANTIBIOTICS, ANTINEOPLASTIC; ANTINEOPLASTIC AGENTS; BENZENESULFONATES; CARCINOMA, HEPATOCELLULAR; CELL DIVISION; CELL LINE, TUMOR; DRUG SYNERGISM; FEEDBACK, PHYSIOLOGICAL; FURANS; HUMANS; LIVER NEOPLASMS; MAP KINASE SIGNALING SYSTEM; MORPHOLINES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; PYRIDINES; PYRIMIDINES; SIROLIMUS; TOR SERINE-THREONINE KINASES; TRANSCRIPTION FACTORS; TRIAZINES;

EID: 84863985238     PISSN: 00224804     EISSN: 10958673     Source Type: Journal    
DOI: 10.1016/j.jss.2011.10.045     Document Type: Article

References (27)

1. J.M. Llovet, A. Burroughs, and J. Bruix Hepatocellular carcinoma Lancet 362 2003 1907
2. J.M. Llovet, and J. Bruix Molecular targeted therapies in hepatocellular carcinoma Hepatology 48 2008 1312
3. A. Lachenmayer, Y. Hoshida, and J.M. Llovet Hippo tumor suppressor pathway: Novel implications for the treatment of hepatocellular carcinoma Gastroenterology 139 2010 692
4. D. Strumberg Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment Drugs Today (Barc) 41 2005 773
5. B. Minguez, V. Tovar, and D. Chiang Pathogenesis of hepatocellular carcinoma and molecular therapies Curr Opin Gastroenterol 25 2009 186
6. M. Chaparro, M.L. Gonzalez, and M. Trapero-Marugan Review article: Pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agents Aliment Pharmacol Ther 28 2008 1269
7. J.M. Llovet, S. Ricci, and V. Mazzaferro Sorafenib in advanced hepatocellular carcinoma N Engl J Med 359 2008 378
8. H. Huynh, V.C. Ngo, and H.N. Koong Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma J Cell Mol Med 13 2009 2673
9. R. Gedaly, P. Angulo, and J. Hundley PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways Anticancer Res 30 2010 4951
10. R. Mallon, L.R. Feldberg, and J. Lucas Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor Clin Cancer Res 17 2011 3193
11. A.M. Venkatesan, C.M. Dehnhardt, and S.E. Delos Bis(morpholino-1,3,5- triazine) derivatives: Potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: Discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor J Med Chem 53 2010 2636
12. F.I. Raynaud, S.A. Eccles, and S. Patel Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: From PI-103 through PI-540, PI-620 to the oral agent GDC-0941 Mol Cancer Ther 8 2009 1725
13. P. Newell, S. Toffanin, and A. Villanueva Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo J Hepatol 51 2009 725
14. K. Yu, C. Shi, and L. Toral-Barza Beyond rapalog therapy: Preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2 Cancer Res 70 2010 621
15. A. Carracedo, L. Ma, and J. Teruya-Feldstein Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer J Clin Invest 118 2008 3065
16. K. Nakanishi, J. Fujimoto, and T. Ueki Hepatocyte growth factor promotes migration of human hepatocellular carcinoma via phosphatidylinositol 3-kinase Clin Exp Metastasis 17 1999 507
17. D. Kim, S. Shu, and M.D. Coppola Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway PLoS One 5 2010 e9616
18. Z. Yuan, D. Kim, and S. Shu Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120 J Biol Chem 285 2010 3815
19. A. Villanueva, D.Y. Chiang, and P. Newell Pivotal role of mTOR signaling in hepatocellular carcinoma Gastroenterology 135 2008 1972
20. S. Faivre, M. Bouattour, and E. Raymond Novel molecular therapies in hepatocellular carcinoma Liver Int 31 Suppl 1 2011 151
21. D.D. Sarbassov, S.M. Ali, and S. Sengupta Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB Mol. Cell 22 2006 159
22. D.D. Sarbassov, D.A. Guertin, and S.M. Ali Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex Science 307 2005 1098
23. C.Y. Zou, K.D. Smith, and Q.S. Zhu Dual targeting of AKT and mammalian target of rapamycin: A potential therapeutic approach for malignant peripheral nerve sheath tumor Mol Cancer Ther 8 2009 1157
24. X. Wan, B. Harkavy, and N. Shen Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism Oncogene 26 2007 1932
25. J. Chang, Y. Hsu, and P. Kuo Increase of Bax/ Bcl-XL ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line Life Sci 76 2005 1883
26. S.J. Su, N.H. Chow, and M.L. Kung Effects of soy isoflavones on apoptosis induction and G2-M arrest in human hepatoma cells involvement of caspase-3 activation, Bcl-2 and Bcl-XL down-regulation, and Cdc2 kinase activity Nutr Cancer 45 2003 113
27. L. Liu, Y. Cao, and C. Chen Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5 Cancer Res 66 2006 11851