Reversal of P-glycoprotein-mediated multidrug resistance with small interference RNA (siRNA) in leukemia cells |
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Authors: | Peng Zhi Xiao Zhijian Wang Yi Liu Peng Cai Yinglin Lu Shihong Feng Wenli Han Zhong Chao |
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Institution: | The Faculty of Laboratory Medicine, Chongqing Medical University, Chongqing, China. |
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Abstract: | 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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