Drug-resistant human bladder-cancer cells are more sensitive to adenovirus-mediated wild-type p53 gene therapy compared to drug-sensitive cells

✍ Scribed by Toshiro Shirakawa; Ryohei Sasaki; Thomas A. Gardner; Chinghai Kao; Zhu-Jun Zhang; Kazuro Sugimura; Masafumi Matsuo; Sadao Kamidono; Akinobu Gotoh

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 373 KB
• Volume: 94
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.1453

✦ Synopsis

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.