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

✍ Scribed by Hui Lv; Zhimin He; Xiaorong Liu; Jianhui Yuan; Yanhui Yu; Zhuchu Chen

Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
178 KB
Volume
102
Category
Article
ISSN
0730-2312

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✦ Synopsis

Abstract

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 14.6‐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. © 2007 Wiley‐Liss, Inc.

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