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      Recent attempts at RNAi-mediated P-glycoprotein downregulation for reversal of multidrug resistance in cancer.

      1 , ,
      Medicinal research reviews
      Wiley

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          Abstract

          Multidrug resistance (MDR) is among the major mechanisms leading to failure in chemotherapy of cancer patients. The ATP-binding cassette proteins are major contributors to MDR, involved in the active efflux of xenobiotics out of cancer cells. Among them, P-glycoprotein (P-gp) is the most dominant protein involved in the efflux of drugs. For more than 30 years, scientists have searched for the ideal P-gp inhibitor to modulate drug resistance activity of P-gp. This inhibitor should be tissue and cell specific with side effects on other tissues, must not provoke immune responses from the host, should provide sustained inhibition, and must be synthesized readily with low cost. Chemical P-gp inhibitors tested to date, have shown nonspecific toxic effects limiting their clinical applications. Sequence-specific P-gp gene silencing by RNA interference (RNAi) may provide a more effective approach for downregulation of specific protein targets due to high specificity, limited toxicity and immunogenicity, and relative ease in synthesis. RNAi can be implemented by delivery of synthetic small interfering RNAs (siRNAs) or by gene expression of short hairpin RNAs using gene expressing vectors. Specific delivery systems and expression vectors have been designed for this purpose and many researchers have explored their effectiveness for P-gp downregulation. In this report, we review the efficiency of various methods for siRNA delivery and transfection for P-gp downregulation in cancer cells for MDR reversal. Novel ideas and observations by different research groups were discussed for future improvement in this essential field.

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          Author and article information

          Journal
          Med Res Rev
          Medicinal research reviews
          Wiley
          1098-1128
          0198-6325
          Jan 2013
          : 33
          : 1
          Affiliations
          [1 ] Department of Biomedical Engineering, Faculty of Medicine, University of Alberta, Edmonton, Canada.
          Article
          10.1002/med.20244
          21523793
          9e23630d-d7d1-4e40-90f1-3dfb4eacb33e
          © 2011 Wiley Periodicals, Inc.
          History

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