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Neoplasma Vol.61, No.2, p.136-143, 2014
|Title: Inhibition of MEK sensitizes gastric cancer cells to TRAIL-induced apoptosis|
|Author: P. WU, Y. W. CHENG, J. Y. WANG, X. D. ZHANG, L. J. ZHANG|
|Abstract: 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.
|Keywords: gastric cancer, TRAIL, ERK1/2, apoptosis|
|Published online: 02-Dec-2013|
|Year: 2014, Volume: 61, Issue: 2||Page From: 136, Page To: 143|