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

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.