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

Cancer Gene Therapy
Zhi PengZhong Chao Han

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.

References

Feb 1, 1992·Japanese Journal of Cancer Research : Gann·I SugawaraK Ueda
May 15, 1991·Journal of the National Cancer Institute·R PirkerL Havelec
Oct 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·H Hamada, T Tsuruo
Jun 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·D J FitzGeraldI Pastan
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·G J ZamanH J Broxterman
May 1, 1997·Biochemical Society Transactions·B R Williams
Dec 1, 1996·General Pharmacology·O FardelA Guillouzo
Feb 3, 2000·Nature Cell Biology·F Wianny, M Zernicka-Goetz
Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Patrick J PaddisonGregory J Hannon
Mar 23, 2002·Science·Thijn R BrummelkampReuven Agami
May 1, 2002·Nature Biotechnology·Thomas Tuschl
Jul 5, 2002·Nature·Anton P McCaffreyMark A Kay
Sep 21, 2002·Cancer Cell·Thijn R BrummelkampReuven Agami
Jan 16, 2003·Leukemia Research·Yaohong TanChunzheng Yang
Jan 25, 2003·Human Gene Therapy·Toufik Abbas-TerkiPatrick Aebischer
Mar 22, 2003·RNA·Sheila A StewartCarl D Novina
Mar 26, 2003·Journal of Molecular Biology·Dag R SørensenMouldy Sioud

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Citations

May 15, 2013·European Journal of Pharmacology·Yidong FengWenlong Huang
May 14, 2005·Cancer Gene Therapy·Tom C Karagiannis, Assam El-Osta
Jan 6, 2006·Drug Metabolism Reviews·Xianbin TianKim L R Brouwer
Aug 2, 2012·Expert Opinion on Biological Therapy·Wei-Qiong Yang, Yi Zhang
Jan 31, 2006·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·S H Lee, P J Sinko
Jun 7, 2005·Expert Opinion on Biological Therapy·Mini ThomasJianzhu Chen
Jan 6, 2015·Molecular Pharmaceutics·Gemma NavarroVladimir P Torchilin
Dec 13, 2005·Gene Therapy·S I PaiT-C Wu

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