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论文类型：期刊论文

发表时间：2013-10-01

发表刊物：BIOMEDICINE & PHARMACOTHERAPY

收录刊物：SCIE、PubMed、Scopus

卷号：67

期号：8

页面范围：731-736

ISSN号：0753-3322

关键字：MCF-7/ADR; ER stress; BH3 mimetic; Apoptosis; PBcl-2

摘要：Drug resistance in chemotherapy for breast cancer is associated with high levels of P-glycoprotein (P-gp) as well as endoplasmic reticulum (ER) stress. In this paper, we aimed to evaluate the efficacy of a pan-BH3 mimetic S1 on drug-resistant MCF-7/ADR cells, and the roles of S1-induced ER stress in cell death. S1 exhibited greater and faster mitochondrial apoptosis in MCF-7/ADR cells than in MCF-7 cells. We demonstrated by Bax/Bak activation and cyrochrome c release that the p-glycprotein had little influence on S1 entering cells and hitting its targets in MCF-7/ADR cells. An IRE1-mediated ER stress response followed by c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) activation was specifically induced by S1 in MCF-7 cells, but not in MCF-7/ADR cells. Coimmunoprecipitation and western blotting analysis determined that ER stress played a protective role in S1-induced apoptosis by triggering Bcl-2 phosphorylation, which grabbed more pro-apoptotic proteins. The synergism effect of ERK inhibitor PD98059 with S1 confirmed the protective role of ER stress. Defective ER stress in MCF-7/ADR cells confers the more sensitivity toward S1. (C) 2013 Elsevier Masson SAS. All rights reserved.