Overexpression of DcR1 and survivin in genetically modified cells with pleiotropic drug resistance

被引:21
作者
Davidovich, IA [1 ]
Levenson, AS [1 ]
Levenson, VV [1 ]
机构
[1] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
关键词
drug resistance; apoptosis; cycloheximide;
D O I
10.1016/j.canlet.2004.03.026
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A previously identified set of short cDNA fragments (genetic suppressor elements, GSEs) expressed in human HT1080 cells protects them against several chemotherapeutic drugs. We show here that DNA damaging agent cytosine arabinoside can induce apoptosis in GSE-containing drug-resistant derivatives (M 125 cells) of HT1080, suggesting that apoptotic pathways are preserved in M125. We also show that both parental cells and M125 constitutively express Fas ligand and TNF-related apoptosis inducing ligand, thus pre-disposing cells to apoptosis. In both cell lines, induction of apoptosis requires simultaneous treatment with low doses of cycloheximide (CHX) and death ligands, however, drug-resistant M125 are substantially more resistant to this treatment. Expression of survivin and decoy receptor 1 (DcR1) is lower in parental cells and is further decreased by CHX. In resistant M125 cell, both survivin and DcR1 are overexpressed even after CHX treatment, which can explain relative resistance of these cells. Thus, apoptosis remains intact in cells with resistance-inducing GSE, suggesting that apoptosis inhibitors can be targeted by anti-cancer therapy in drug-resistant tumors. (C) 2004 Published by Elsevier Ireland Ltd.
引用
收藏
页码:189 / 197
页数:9
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