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

Toshiro Shirakawa, Ryohei Sasaki, Thomas A. Gardner, Chinghai Kao, Zhu Jun Zhang, Kazuro Sugimura, Masafumi Matsuo, Sadao Kamidono, Akinobu Gotoh

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 G1 cell-cycle 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-β-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.

Original languageEnglish (US)
Pages (from-to)282-289
Number of pages8
JournalInternational Journal of Cancer
Volume94
Issue number2
DOIs
StatePublished - Oct 15 2001

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Keywords

  • Adenovirus
  • Bladder cancer
  • Drug resistance
  • Gene therapy
  • Gene transfer
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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