We investigated the therapeutic potential and molecular mechanism of adenovirus-mediated wt p53 gene therapy for drug-resistant human bladder cancers. KK47, a human bladder-cancer cell line, along with the drug-resistant sublines KK47/DDP10, KK47/DDP20 (cisplatin-resistant) and KK47/ ADM (doxorubicin-resistant) were used for the experiments. All 4 KK47 cell lines had genetically normal p53 genes. Using an in vitro cytotoxicity assay, the drug-resistant cell lines were more sensitive to Ad-CMV-p53 cell killing than the KK47 parental cell line. Ad-CMV-p53 induced higher levels of p53 protein and mRNA in the drug-resistant cell lines than in the parental cell line and, consequently, higher levels of p21 and Bax mRNA, which resulted in higher percentages of G 1 cellcycle arrest and apoptosis. The higher efficiencies of adenoviral gene transfer in the drug-resistant cell lines were confirmed by X-gal staining after infection with Ad-CMV-␤-gal. In conclusion, adenovirus-mediated wt p53 gene therapy was more effective in the drug-resistant bladder-cancer cell lines than in the drug-sensitive bladder-cancer cell line.

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Adenoviral-mediated HGF gene transfer into the testis in the cryptorchidism rats inhibited germ cell apoptosis and restored spermatogenesis.

The results suggest that further investigation of molecular gene therapy with recombinant wt-p53 adenovirus for the treatment of BPH is warranted.