Inhibition of proteasome activity sensitizes human granulosa tumor cells to TRAIL-induced cell death

被引:16
作者
Woods, Dori C. [1 ,2 ]
Liu, Han-Ken [1 ,2 ]
Nishi, Yoshihiro [3 ]
Yanase, Toshihiko [3 ]
Johnson, A. L. [1 ,2 ]
机构
[1] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA
[2] Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA
[3] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 8128582, Japan
关键词
granulosa cell tumors; TRAIL; proteasome; p53; apoptosis;
D O I
10.1016/j.canlet.2007.10.016
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:20 / 27
页数:8
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