首页 | 本学科首页   官方微博 | 高级检索  
     


5‐Nitro‐2‐(3‐Phenylpropylamino) Benzoic Acid Induced Drug Resistance to Cisplatin in Human Erythroleukemia Cell Lines
Authors:Ye Xu  Hua Zheng  Jin‐Song Kang  Lei Zhang  Jing Su  Hong‐Yan Li  Lian‐Kun Sun
Affiliation:1. Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, China;2. Medical Research Laboratory, Jilin Medical College, Jilin City, China;3. Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, ChinaFax: 086‐431‐85619402
Abstract:
Mechanisms of cisplatin resistance in cancer cells are not fully understood. Here, we showed a critical role for the chloride channel‐3 (ClC‐3) in cisplatin resistance in human erythroleukemia K562 and RK562 cells. We found that a chloride channel blocker 5‐nitro‐2‐(3‐phenylpropylamino) benzoic acid (NPPB) could protect cells from cisplatin‐induced apoptosis. NPPB treatment decreased the mRNA and the protein expression of Bax/Bcl‐2, decreased the protein expressions of cytochrome C and caspase‐3, and increased the mRNA expressions of cyclin D1 and ClC‐3 in cells treated with cisplatin. The caspase‐3 activity was decreased significantly and the rate of cell apoptosis was decreased. NPPB treatment increased CIC‐3 expression, which could increase acidification of intracellular compartments, and increased sequestration of cisplatin, inducing decreased effective drug concentrations, and subsequently cell death. Collectively, our data indicate that NPPB can induce drug resistance to cisplatin by upregulating the expression of CIC‐3. NPPB‐induced CIC‐3 expression facilitates acidification of sequestrated cisplatin, and plays an important role in preventing cisplatin‐induced apoptosis in human erythroleukemia K562 and RK562 cells. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.
Keywords:chemotherapy  resistance  cisplatin  apoptosis  NPPB  ClC‐3
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号