Neoplasma. 2014;61(2):136-43. doi: 10.4149/neo_2014_019.
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.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）长期以来被认为在诱导癌细胞凋亡方面具有高度选择性，但事实证明它是一种能诱导更广泛的多种效应的分子。本研究旨在探讨 ERK1/2 通路是否参与 TRAIL 对胃癌细胞的抗肿瘤作用。TRAIL 除了激活外源性和内源性凋亡途径外，还触发了 ERK1/2 的激活。MEK 抑制剂 U0126 抑制 ERK1/2 信号通路，通过增加 caspase 的激活、线粒体膜电位下降和 XIAP、cIAP2 和 Mcl-1 的下调，促进细胞死亡。这些结果表明，TRAIL 诱导的 ERK1/2 的快速激活可能是一种在早期对抗 TRAIL 攻击的生存机制，抑制 ERK1/2 信号通路可以使胃癌细胞对 TRAIL 诱导的凋亡敏感。
