Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death
Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death
复制标题
DOI：
10.1016/j.canlet.2007.10.016
复制
发表时间：
2008-02-18
期刊：
影响因子：
9.7
通讯作者：
Johnson, A. L.
中科院分区：
文献类型：
--
作者：
Woods, Dori C.;Liu, Han-Ken;Johnson, A. L.
利用人颗粒肿瘤细胞（GCT）系（KGN和COV434）在体外建立TRAIL和蛋白酶体抑制剂对细胞活力的联合影响。TRAIL诱导两种细胞系的活力轻微但一致地下降，使用Z-LLF- cho （Z-LLF）对蛋白酶体活性进行药理学抑制，协同增强了TRAIL诱导的活力丧失。这种增强的致敏性与TRAIL受体、DR5和促凋亡Bax的上调有关。对p53表达的靶向降低表明，Z-LLF增强DR5和Bax表达的能力与p53活性无关。这些研究强调了利用已建立的细胞系开发针对gct的靶向治疗的潜力。2007爱思唯尔爱尔兰有限公司版权所有。
Human granulosa tumor cell (GCT) lines (KGN and COV434) were utilized to establish the combinatorial effects of TRAIL treatment and a proteasome inhibitor on cell viability, in vitro. TRAIL induced a slight, but consistent, decrease in viability for both cell lines, and pharmacologic inhibition of proteasome activity, using Z-LLF-CHO (Z-LLF), synergistically enhanced TRAIL-induced loss of viability. This enhanced sensitization was associated with the up-regulation of a TRAIL receptor, DR5, and pro-apoptotic Bax. Targeted reduction of p53 expression revealed that the ability of Z-LLF to enhance DR5 and Bax expression occurs independent of p53 activity. These studies underscore the potential to develop targeted treatments for GCTs using established cell lines. (C) 2007 Elsevier Ireland Ltd. All rights reserved.