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Eur J Pharmacol. 2006 Apr 24;536(1-2):93-7. Epub 2006 Mar 3.

Reversal of MDR1 gene-dependent multidrug resistance using low concentration of endonuclease-prepared small interference RNA.

Author information

1
Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai 200433, China.

Abstract

Multidrug resistance following initial chemotherapy is commonly associated with MDR1 gene encoding for P-glycoprotein (P-gp). RNA interference of MDR1 gene expression was used as a strategy to reverse MDR1-mediated multidrug resistance phenotypes. Here we report that endonuclease-prepared small interfering RNA (esiRNA) at concentrations as low as 10 ng/ml (about 0.7 nM) can decrease MDR1 expression and increase chemosensitivity in the Adriamycin-induced resistant MCF-7/R cells. When MCF-7/R cells were transiently transfected with esiRNA of MDR1 (esiMDR1), the MDR1 mRNA was reduced by about 50%, drug accumulation increased by about 30%, and the IC50 for daunorubicin was reduced from 4.5 to 1.2 microM. These results provide evidence that esiRNA of MDR1 could be an alternative to P-gp inhibitors with the advantage of avoiding non-specific suppression with a lower effective dosage than using a single siRNA duplex, offering a potential therapeutic application of siRNA.

PMID:
16564522
DOI:
10.1016/j.ejphar.2006.02.050
[Indexed for MEDLINE]

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