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

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.

journal_name

J Cell Biochem

authors

Lv H,He Z,Liu X,Yuan J,Yu Y,Chen Z

doi

10.1002/jcb.21276

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

75-81

issue

1

eissn

0730-2312

issn

1097-4644

journal_volume

102

pub_type

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