Reversal of multidrug resistance in renal cell carcinoma by short hairpin RNA targeting MDR1 gene

Chin Med J (Engl). 2012 Aug;125(15):2741-5.

Abstract

Background: Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, confers multidrug resistance (MDR) in renal cell carcinoma (RCC) and is a major reason for unsuccessful chemotherapy. This study aimed to determine the effct of RNA interference (RNAi) on the reversal of MDR in human RCC.

Methods: We designed and selected one short hairpin RNA (shRNA) targeting MDR1 gene, which is stably expressed from integrated plasmid and transfected by lentivirus fluid in human RCC A498 cell.

Results: The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P < 0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line.

Conclusion: MDR could be reversed by RNAi in human RCC A498 cell line, which may be used for clinical application in future.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Inhibitory Concentration 50
  • Lentivirus / genetics
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • RNA, Small Interfering