Fiber-modified adenovirus-mediated suicide gene therapy can efficiently eliminate bladder cancer cells in vitro and in vivo

Abstract

Adenovirus-mediated gene therapy is a promising strategy for bladder cancer treatment. However, the loss of the coxsackie and adenovirus receptor (CAR) in bladder cancer cells decreases the infection efficiency of the therapeutic adenovirus. In this study, we constructed an Arg-Gly-Asp (RGD)-modified adenovirus, RGDAd-UPII-TK, that carries a suicide gene called HSV-TK that is driven by a human UPII promoter. Then, we tested the bladder cancer specificity of the UPII promotor and the expression of the HSV-TK protein. Additionally, we observed a potent cytotoxic effects of RGDAd-UPII-TK and ganciclovir (GCV) on bladder cancer as demonstrated by reduced cell survival and morphology changes in vitro. Furthermore, we confirmed that RGDAd-UPII-TK in combination with a GCV injection could significantly reduce the established T24 tumor growth and increase apoptosis in vivo. Altogether, our results indicated that the recombinant adenovirus RGDAd-UPII-TK could target bladder cancer through valid gene therapy.