Combination of MEK Inhibitor and the JAK2-STAT3 Pathway Inhibition for the Therapy of Colon Cancer.
作者： Jianying Jin , Qunyi Guo , Jingjing Xie , Dan Jin , Yanan Zhu
DOI: 10.1007/S12253-019-00592-6
关键词:
摘要: The study aimed to investigate the reason of HCT116 cell resistance MEK inhibitor, and combination treatment effects inhibitor AZD6244 JAK2/STAT3 AG490 on colon cancer in vitro vivo, including viability, apoptosis, explore partial mechanisms focused promoted activation JAK2-STAT3 pathways. In vitro, we examined viability by CCK8, apoptosis flow cytometry; Western blot measured p-ERK, p-JAK2, p-STAT3 STAT3 expression. nude mice were subcutaneously injected cells. tumor volume weight detected. AZD6244, which inhibited ERK signaling. significantly induced completely Combination had a stronger effect than that as monotherapy vivo. K-Ras mutations cells synergistically increases Collectively, these results provide rationale for combining inhibitors JAK/STAT pathway reduce potential impact drug resistance.
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Jennifer S Lin, Elizabeth M Webber, Caitlyn A Senger, Rebecca S Holmes, Evelyn P Whitlock, Systematic review of pharmacogenetic testing for predicting clinical benefit to anti-EGFR therapy in metastatic colorectal cancer American Journal of Cancer Research. ,vol. 1, pp. 650- 662 ,(2011)
Christopher J. Caunt, Matthew J. Sale, Paul D. Smith, Simon J. Cook, MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road Nature Reviews Cancer. ,vol. 15, pp. 577- 592 ,(2015) , 10.1038/NRC4000
Walter J. Jessen, Shyra J. Miller, Edwin Jousma, Jianqiang Wu, Tilat A. Rizvi, Meghan E. Brundage, David Eaves, Brigitte Widemann, Mi-Ok Kim, Eva Dombi, Jessica Sabo, Atira Hardiman Dudley, Michiko Niwa-Kawakita, Grier P. Page, Marco Giovannini, Bruce J. Aronow, Timothy P. Cripe, Nancy Ratner, MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors Journal of Clinical Investigation. ,vol. 123, pp. 340- 347 ,(2013) , 10.1172/JCI60578
Matthew Holderfield, Marian M. Deuker, Frank McCormick, Martin McMahon, Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond Nature Reviews Cancer. ,vol. 14, pp. 455- 467 ,(2014) , 10.1038/NRC3760
Matteo S Carlino, Jason R Todd, Kavitha Gowrishankar, Branka Mijatov, Gulietta M Pupo, Carina Fung, Stephanie Snoyman, Peter Hersey, Georgina V Long, Richard F Kefford, Helen Rizos, None, Differential activity of MEK and ERK inhibitors in BRAF inhibitor resistant melanoma. Molecular Oncology. ,vol. 8, pp. 544- 554 ,(2014) , 10.1016/J.MOLONC.2014.01.003
Yujie Zhao, Alex A. Adjei, The clinical development of MEK inhibitors Nature Reviews Clinical Oncology. ,vol. 11, pp. 385- 400 ,(2014) , 10.1038/NRCLINONC.2014.83
Denise A. Chan, Amato J. Giaccia, Harnessing synthetic lethal interactions in anticancer drug discovery Nature Reviews Drug Discovery. ,vol. 10, pp. 351- 364 ,(2011) , 10.1038/NRD3374
Kevin M Haigis, Krystle R Kendall, Yufang Wang, Ann Cheung, Marcia C Haigis, Jonathan N Glickman, Michiko Niwa-Kawakita, Alejandro Sweet-Cordero, Judith Sebolt-Leopold, Kevin M Shannon, Jeffrey Settleman, Marco Giovannini, Tyler Jacks, Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon Nature Genetics. ,vol. 40, pp. 600- 608 ,(2008) , 10.1038/NG.115
D. van der Hoeven, K.-j. Cho, X. Ma, S. Chigurupati, R. G. Parton, J. F. Hancock, Fendiline Inhibits K-Ras Plasma Membrane Localization and Blocks K-Ras Signal Transmission Molecular and Cellular Biology. ,vol. 33, pp. 237- 251 ,(2013) , 10.1128/MCB.00884-12
Cecily P. Vaughn, Scott D. ZoBell, Larissa V. Furtado, Christine L. Baker, Wade S. Samowitz, Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes, Chromosomes and Cancer. ,vol. 50, pp. 307- 312 ,(2011) , 10.1002/GCC.20854