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 Citations (Scopus)

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

Fingerprint

p53 Genes
Urinary Bladder Neoplasms
Adenoviridae
Genetic Therapy
Cell Line
Pharmaceutical Preparations
G1 Phase Cell Cycle Checkpoints
Messenger RNA
Doxorubicin
Cisplatin
Apoptosis
Staining and Labeling
Infection

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Drug-resistant human bladder-cancer cells are more sensitive to adenovirus-mediated wild-type p53 gene therapy compared to drug-sensitive cells. / Shirakawa, Toshiro; Sasaki, Ryohei; Gardner, Thomas A.; Kao, Chinghai; Zhang, Zhu Jun; Sugimura, Kazuro; Matsuo, Masafumi; Kamidono, Sadao; Gotoh, Akinobu.

In: International Journal of Cancer, Vol. 94, No. 2, 15.10.2001, p. 282-289.

Research output: Contribution to journalArticle

Shirakawa, Toshiro ; Sasaki, Ryohei ; Gardner, Thomas A. ; Kao, Chinghai ; Zhang, Zhu Jun ; Sugimura, Kazuro ; Matsuo, Masafumi ; Kamidono, Sadao ; Gotoh, Akinobu. / Drug-resistant human bladder-cancer cells are more sensitive to adenovirus-mediated wild-type p53 gene therapy compared to drug-sensitive cells. In: International Journal of Cancer. 2001 ; Vol. 94, No. 2. pp. 282-289.
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