Silencing of CXCR4 by RNA interference inhibits cell growth and metastasis in human renal cancer cells.

Renal cell carcinoma (RCC) is the third most common genitourinary malignancy, accounting for 3% of cancer in adults. The mortality and morbidity of RCC is strongly associated with its high propensity to metastasize to specific organs. This may be attributed to the fact that the CXCR4 G protein-coupled receptor (GPCR) on RCC cells mediates chemoattraction toward stromal-derived factor 1 (SDF-1) secreted by target organs. RNA interference (RNAi), which has been proven to be a powerful tool for suppressing gene expression, may lead to novel strategies for treating RCC. Our previous experiments confirmed that RCC A-498 cells overexpressing CXCR4 are associated with increased invasiveness. In this study, we constructed recombinant CXCR4-RNAi plasmids and transfected them into A-498 cells in vitro. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting revealed that CXCR4 was downregulated in transfected cells compared with control cells. Our results from MTT and transwell migration assays indicated that specific downregulation of CXCR4 inhibited cell growth, invasiveness and migration. Flow cytometric analysis indicated that silencing of CXCR4 in A-498 cells by RNA interference induced cell apoptosis in RCC in vitro. Thus, siRNA targeting of CXCR4 can effectively inhibit the growth and metastasis of RCC cells and may be a promising innovative anticancer therapy.