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

Cancer Gene Therapy volume 11, pages 707–712 (2004)Cite this article

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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Acknowledgements

We thank Professor Chunzheng Yang for providing the cell line K562/A02 and Ms Ming Feng for technical assistance. This work is supported by grants of 863 (2001AA215311, 2002AA223354) and 973 (001CB5101) from the Ministry of Science & Technology of China to Han ZC.

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Authors and Affiliations

  1. The Faculty of Laboratory Medicine, Chongqing Medical University, Chongqing, China

    Zhi Peng & Wenli Feng

  2. State Key Laboratory of Experiment Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China

    Zhijian Xiao, Yi Wang, Peng Liu, Yinglin Cai, Shihong Lu & Zhong Chao Han

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  1. Zhi Peng
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Correspondence to Zhong Chao Han.

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Peng, Z., Xiao, Z., Wang, Y. et al. Reversal of P-glycoprotein-mediated multidrug resistance with small interference RNA (siRNA) in leukemia cells. Cancer Gene Ther 11, 707–712 (2004). https://doi.org/10.1038/sj.cgt.7700738

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