Growth inhibition of a tongue squamous cell carcinoma cell line (Tca8113) in vitro and in vivo via siRNA-mediated down-regulation of skp2.

Human S-phase kinase-associated protein (skp) 2, the specific ubiquitin ligase subunit that targets the negative regulator p27(Kip1) of the cell cycle and brings about its degradation, is overexpressed in various cancers, including human oral squamous cell carcinomas; its expression levels are inversely related to those of p27(Kip1) in these cells. Recently, a technique known as RNA interference (RNAi) has successfully been applied to mammalian cells. In order to evaluate the applications of the RNAi strategy for cancer gene therapy, the authors treated Tca8113 cells expressing high levels of Skp2 with a small interfering RNA (siRNA) expression plasmid vector targeting skp2 in vitro and in vivo. They demonstrated that the Skp2 protein levels decreased, while the p27(Kip1) protein levels increased in Tca8113 cells transfected with skp2siRNA. Further, skp2siRNA inhibited growth in the Tca8113 cells in vitro and suppressed tumor proliferation in vivo. These results suggest that siRNA-mediated silencing of the skp2 gene may represent a useful strategy for gene therapy of tumors expressing high levels of Skp2.