Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 536, Issue 1-2, Pages 93-97Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2006.02.050
Keywords
multidrug resistance; MDR1; endonuclease-prepared small interference; RNA (esiRNA); low concentration of esiRNA
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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 mu M. 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. (c) 2006 Elsevier B.V. All rights reserved.
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