Inhibition of MEK sensitizes gastric cancer cells to TRAIL-induced apoptosis

被引：3
作者：
Wu, P. [1 ]
Cheng, Y. W. [1 ]
Wang, J. Y. [1 ]
Zhang, X. D. [2 ]
Zhang, L. J. [1 ]
机构：
[1] Anhui Med Univ, Dept Immunol, Hefei 230032, Anhui, Peoples R China
[2] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia
来源：
NEOPLASMA | 2014年 / 61卷 / 02期
基金：
中国国家自然科学基金;
关键词：
gastric cancer; TRAIL; ERK1/2; apoptosis; PROTECTS MELANOMA-CELLS; HUMAN GLIOMA-CELLS; INDEPENDENT APOPTOSIS; LIGAND RESISTANCE; DOWN-REGULATION; UP-REGULATION; ER STRESS; MCL-1; ACTIVATION; ERK1/2;
D O I：
10.4149/neo_2014_019
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which has long been believed to be highly selective in inducing apoptosis in cancer cells, has turned out to be a molecule that induces a far more diverse range of effects. The aim of this study was to investigate whether or not ERK1/2 pathway is involved in antitumor effects of TRAIL on gastric cancer cells. In addition to activate the extrinsic and intrinsic apoptotic pathway, TRAIL also triggered the activation of ERK1/2. Inhibition of ERK1/2 signaling by MEK inhibitor U0126 promoted cell death via increased activation of caspases, drop in mitochondrial membrane potential and downregulation of XIAP, cIAP2 and Mcl-1. These results indicate that TRAIL-induced rapid activation of ERK1/2 may be a survival mechanism to struggle against TRAIL assault at the early stage, and inhibition of ERK1/2 signaling can sensitize gastric cancer cells to TRAIL-induced apoptosis.
引用
收藏
页码：136 / 143
页数：8
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