Reversal of BCRP-mediated multidrug resistance by stable expression of small interfering RNAs

被引:16
作者
Lv, Hui [1 ]
He, Zhimin [1 ]
Liu, Xiaorong [1 ]
Yuan, Jianhui [1 ]
Yu, Yanhui [1 ]
Chen, Zhuchu [1 ]
机构
[1] Cent S Univ, Xiangya Med Sch, Canc Res Inst, Hunan, Peoples R China
关键词
breast cancer resistance (BCRP); multidrug resistance; RNAi;
D O I
10.1002/jcb.21276
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Breast cancer resistance protein (BCRP) is an ATP-binding cassette multidrug transporter that confers resistance to various anticancer drugs like Mitoxantrone. Overexpression of BCRP confers multidrug resistance (MDR) in cancer cells and is a frequent impediment to successful chemotherapy. For stable reversal of BCRP-depending MDR by RNA interference technology, a hU6-RNA gene promoter-driven expression vector encoding anti-BCRP short hairpin RNA (shRNA) molecules was constructed. By treating endogenously and exogenously expresses high levels of BCRP cells with these constructs, expression of the targeted BCRP-encoding mRNA, and transport protein was inhibited completely. Furthermore, the accumulation of mitoxantrone in the anti-BCRP shRNA-treated cells increased. And the sensitivity to mitoxantrone of anti-BCRP shRNA-treated cells is increased 14.0-fold and 2.44-fold respectively compared to their control (P< 0.05). These data indicated that stable shRNA-mediated RNAi could be tremendously effective in reversing BCRP-mediated MDR and showed promises in overcoming MDR by gene therapeutic applications. J. Cell. Biochem. 102: 75-81,2007. (C) 2007Wiley-Liss, Inc.
引用
收藏
页码:75 / 81
页数:7
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