Enhancing therapeutic efficacy of the MEK inhibitor, MEK162, by blocking autophagy or inhibiting PI3K/Akt signaling in human lung cancer cells

Cancer Letters

Volumn 364, Issue 1, 2015, Pages 70-78

  Yao, Weilong ^a,b   Yue, Ping ^b   Zhang, Guojing ^b   Owonikoko, Taofeek K ^b   Khuri, Fadlo R ^b   Sun, Shi Yong ^b  

^a Central South University   (China)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autophagy; BKM120; Lung cancer; MEK162

Indexed keywords

BINIMETINIB; BUPARLISIB; CHLOROQUINE; SELUMETINIB; BENZIMIDAZOLE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER CELL; CANCER COMBINATION CHEMOTHERAPY; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CELL GROWTH; CONCENTRATION RESPONSE; DRUG MECHANISM; DRUG STRUCTURE; G1 PHASE CELL CYCLE CHECKPOINT; GENE MUTATION; GROWTH INHIBITION; HUMAN; HUMAN CELL; IC50; LUNG CANCER; MOUSE; NONHUMAN; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; ENZYMOLOGY; LUNG TUMOR; METABOLISM; NON SMALL CELL LUNG CANCER; PATHOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

AUTOPHAGY; BENZIMIDAZOLES; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; HUMANS; LUNG NEOPLASMS; MAP KINASE KINASE KINASES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION;

EID: 84929655856     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2015.04.028     Document Type: Article

References (29)

1. Stinchcombe T.E., Johnson G.L. MEK inhibition in non-small cell lung cancer. Lung Cancer 2014, 86:121-125.
2. Janne P.A., Shaw A.T., Pereira J.R., Jeannin G., Vansteenkiste J., Barrios C., et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 2013, 14:38-47.
3. Thumar J., Shahbazian D., Aziz S.A., Jilaveanu L.B., Kluger H.M. MEK targeting in N-RAS mutated metastatic melanoma. Mol. Cancer 2014, 13:45.
4. Hamidi H., Lu M., Chau K., Anderson L., Fejzo M., Ginther C., et al. KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition. Br. J. Cancer 2014, 111:1788-1801.
5. Chen X., Wu Q., Tan L., Porter D., Jager M.J., Emery C., et al. Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations. Oncogene 2014, 33:4724-4734.
6. Ran L., Sirota I., Cao Z., Murphy D., Chen Y., Shukla S., et al. Combined Inhibition of MAP Kinase and KIT signaling synergistically destabilizes ETV1 and suppresses GIST Tumor growth. Cancer Discov 2015, 5:304-315.
7. Zhang J., Hong Y., Shen J. Combination treatment with perifosine and MEK-162 demonstrates synergism against lung cancer cells in vitro and in vivo. Tumour Biol 2015, epub ahead of print.
8. Ascierto P.A., Schadendorf D., Berking C., Agarwala S.S., van Herpen C.M., Queirolo P., et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol 2013, 14:249-256.
9. Ren H., Chen M., Yue P., Tao H., Owonikoko T.K., Ramalingam S.S., et al. The combination of RAD001 and NVP-BKM120 synergistically inhibits the growth of lung cancer in vitro and in vivo. Cancer Lett 2012, 325:139-146.
10. Xu C.X., Zhao L., Yue P., Fang G., Tao H., Owonikoko T.K., et al. Augmentation of NVP-BEZ235's anticancer activity against human lung cancer cells by blockage of autophagy. Cancer Biol. Ther 2011, 12:549-555.
11. Sun S.Y., Yue P., Dawson M.I., Shroot B., Michel S., Lamph W.W., et al. Differential effects of synthetic nuclear retinoid receptor-selective retinoids on the growth of human non-small cell lung carcinoma cells. Cancer Res 1997, 57:4931-4939.
12. Wang X., Hawk N., Yue P., Kauh J., Ramalingam S.S., Fu H., et al. Overcoming mTOR inhibition-induced paradoxical activation of survival signaling pathways enhances mTOR inhibitors' anticancer efficacy. Cancer Biol. Ther 2008, 7:1952-1958.
13. Sun S.Y., Yue P., Shroot B., Hong W.K., Lotan R. Induction of apoptosis in human non-small cell lung carcinoma cells by the novel synthetic retinoid CD437. J. Cell. Physiol 1997, 173:279-284.
14. Sun S.Y., Zhou Z., Wang R., Fu H., Khuri F.R. The farnesyltransferase inhibitor Lonafarnib induces growth arrest or apoptosis of human lung cancer cells without downregulation of Akt. Cancer Biol. Ther 2004, 3:1092-1098. discussion 1099-1101.
15. Liu X., Yue P., Zhou Z., Khuri F.R., Sun S.Y. Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells. J. Natl. Cancer Inst 2004, 96:1769-1780.
16. Sun S.Y., Yue P., Wu G.S., El-Deiry W.S., Shroot B., Hong W.K., et al. Mechanisms of apoptosis induced by the synthetic retinoid CD437 in human non-small cell lung carcinoma cells. Oncogene 1999, 18:2357-2365.
17. Janku F., McConkey D.J., Hong D.S., Kurzrock R. Autophagy as a target for anticancer therapy. Nat. Rev. Clin. Oncol 2011, 8:528-539.
18. Corcoran R.B., Rothenberg S.M., Hata A.N., Faber A.C., Piris A., Nazarian R.M., et al. TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF-mutant melanoma. Sci. Transl. Med 2013, 5:196ra198.
19. Turke A.B., Song Y., Costa C., Cook R., Arteaga C.L., Asara J.M., et al. MEK inhibition leads to PI3K/AKT activation by relieving a negative feedback on ERBB receptors. Cancer Res 2012, 72:3228-3237.
20. Gopal Y.N., Deng W., Woodman S.E., Komurov K., Ram P., Smith P.D., et al. Basal and treatment-induced activation of AKT mediates resistance to cell death by AZD6244 (ARRY-142886) in Braf-mutant human cutaneous melanoma cells. Cancer Res 2010, 70:8736-8747.
21. Casimiro M.C., Velasco-Velazquez M., Aguirre-Alvarado C., Pestell R.G. Overview of cyclins D1 function in cancer and the CDK inhibitor landscape: past and present. Expert Opin. Investig. Drugs 2014, 23:295-304.
22. Levine B., Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008, 132:27-42.
23. Garon E.B., Finn R.S., Hosmer W., Dering J., Ginther C., Adhami S., et al. Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines. Mol. Cancer Ther 2010, 9:1985-1994.
24. Irving J., Matheson E., Minto L., Blair H., Case M., Halsey C., et al. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood 2014, 124:3420-3430.
25. Hofmann I., Weiss A., Elain G., Schwaederle M., Sterker D., Romanet V., et al. K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo. PLoS ONE 2012, 7:e44146.
26. Balmanno K., Chell S.D., Gillings A.S., Hayat S., Cook S.J. Intrinsic resistance to the MEK1/2 inhibitor AZD6244 (ARRY-142886) is associated with weak ERK1/2 signalling and/or strong PI3K signalling in colorectal cancer cell lines. Int. J. Cancer 2009, 125:2332-2341.
27. Yeh J.J., Routh E.D., Rubinas T., Peacock J., Martin T.D., Shen X.J., et al. KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer. Mol. Cancer Ther 2009, 8:834-843.
28. Roux P.P., Shahbazian D., Vu H., Holz M.K., Cohen M.S., Taunton J., et al. RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation. J. Biol. Chem 2007, 282:14056-14064.
29. Mendoza M.C., Er E.E., Blenis J. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem. Sci 2011, 36:320-328.