Reversal of P-glycoprotein-mediated multidrug resistance with small interference RNA (siRNA) in leukemia cells

被引：0
作者：
Zhi Peng
Zhijian Xiao
Yi Wang
Peng Liu
Yinglin Cai
Shihong Lu
Wenli Feng
Zhong Chao Han
机构：
[1] The Faculty of Laboratory Medicine,
[2] Chongqing Medical University,undefined
[3] State Key Laboratory of Experiment Hematology,undefined
[4] Institute of Hematology,undefined
[5] Chinese Academy of Medical Sciences and Peking Union Medical College,undefined
来源：
Cancer Gene Therapy | 2004年 / 11卷
关键词：
small interference RNA; mdr-1 gene; k562/A02 cell lineleukemia; multidrug resistance;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
The multidrug resistance (MDR) mediated by P-glycoprotein (P-gp), the MDR1 gene product, is one of the major obstacles in leukemia treatment. The present study was designed to explore a MDR1-targeted small interfering RNA (si-MDR1) approach for reversal of P-gp-mediated MDR in the MDR human leukemia cell line k562/A02. It was found that si-MDR1 significantly inhibited MDR1 expression at both mRNA and protein levels. Depletion of MDR1 by si-MDR1 correlated with the increased sensitivity of the cells to cytotoxic agents and with the enhanced intracellular retention of daunorubicin (DNR). One base-pair mutated control (si-MDR1-Mut) lost the effect of si-MDR1 on both the degradation of mdr1 mRNA and the reduction of P-gp expression. These findings indicate that siRNA specifically and efficiently interferes with the expression of mdr1 and could be used as a molecularly defined therapeutic approach for MDR in the treatment of leukemia.
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页码：707 / 712
页数：5
相关论文
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