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Drug‐resistant human bladder‐cancer cells are more sensitive to adenovirus‐mediated wild‐type p53 gene therapy compared to drug‐sensitive cells
Author(s) -
Shirakawa Toshiro,
Sasaki Ryohei,
Gardner Thomas A.,
Kao Chinghai,
Zhang ZhuJun,
Sugimura Kazuro,
Matsuo Masafumi,
Kamidono Sadao,
Gotoh Akinobu
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1453
Subject(s) - cell culture , cisplatin , genetic enhancement , cancer research , doxorubicin , bladder cancer , cell , biology , apoptosis , cancer , cell cycle , drug resistance , adenoviridae , microbiology and biotechnology , chemotherapy , gene , genetics
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 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. © 2001 Wiley‐Liss, Inc.