RNA-interference-mediated Cdc42 silencing down-regulates phosphorylation of STAT3 and suppresses growth in human bladder-cancer cells

Cdc42 (cell division cycle 42), a member of Rho GTPases, is involved in cell transformation, proliferation, survival, invasion and metastasis of human cancer cells. Here, RNAi (RNA interference)-mediated gene silencing was used to investigate the roles of Cdc42 and to assess its therapeutic potential in human bladder cancer. The results showed that Cdc42 silencing resulted in a marked reduction of Cdc42 mRNA and protein expression and a significant inhibition of cell proliferation from G(0)/G(1)- to S-phase in two (E) and T24) human bladder-cancer cell lines. Moreover, RNAi-mediated inhibition of Cdc42 induced apoptosis of EJ cells 96 h after transfection. In addition, we found that silencing of Cdc42 could down-regulate the level of phosphorylated STAT3 (signal transducer and activator of transcription 3), but did not influence the level of total STAT3 in the two bladder-cancer cell lines. These results suggest that RNAi-mediated Cdc42 silencing may be a novel approach for gene therapy of bladder cancer.