Overexpression of bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer

ABSTRACT To investigate the effects of the expression of Bcl-2 protein in bladder cancer on the apoptosis induced by cisplatin or adenoviral-mediated _P53_ gene (Ad5CMV-_P53_) transfer, we

transfected the _BCL-2_ gene into KoTCC-1, a human bladder cancer cell line that does not express the Bcl-2 protein. The Bcl-2-transfected KoTCC-1 (KoTCC-1/B) exhibited significantly higher

resistance to both cisplatin and Ad5CMV-_P53_ transfer than did either the parental KoTCC-1 (KoTCC-1/P) or the vector-only transfected cell line (KoTCC-1/C). The flow cytometric analysis of

the propidium iodide-stained nuclei and DNA fragmentation analysis after cisplatin or Ad5CMV-_P53_ treatment revealed DNA degradation in both KoTCC-1/P and KoTCC-1/C, whereas KoTCC1/B showed

a marked inhibition of DNA degradation. Following the treatment with cisplatin or Ad5CMV-_P53_, the accumulation of p53 protein was highly detectable for a long period in KoTCC-1/B compared

to that in KoTTC-1/P and KoTCC-1/C. Furthermore, the cisplatin and Ad5CMV-_P53_ treatments each reduced the volume of the subcutaneous tumors established in nude mice formed by KoTCC-1/P or

KoTCC-1/C; in contrast, their reductive effects on the tumors formed by KoTCC-1/B were significantly suppressed. The intraperitoneal tumor cell implantation model revealed that the

prognoses of mice injected with KoTCC-1/B were significantly inferior to those of the mice injected with either KoTCC-1/P or KoTCC-1/C after treatment with cisplatin or Ad5CMV-_P53_. These

findings suggest that the expression of Bcl-2 in bladder cancer cells interferes with the therapeutic effects of cisplatin and Ad5CMV-_P53_ through the inhibition of the apoptotic pathway.

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AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto, 860, Japan Hideaki Miyake, Norihisa

Hanada, Hideo Nakamura & Hideyuki Saya * Department of Urology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650, Japan Hideaki Miyake, Isao Hara, Hiroshi Eto, 

Kazuo Gohji, Soichi Arakawa & Sadao Kamidono * First Department of Surgery, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, 700, Japan Shunsuke Kagawa & Toshiyoshi

Fujiwara Authors * Hideaki Miyake View author publications You can also search for this author inPubMed Google Scholar * Norihisa Hanada View author publications You can also search for this

author inPubMed Google Scholar * Hideo Nakamura View author publications You can also search for this author inPubMed Google Scholar * Shunsuke Kagawa View author publications You can also

search for this author inPubMed Google Scholar * Toshiyoshi Fujiwara View author publications You can also search for this author inPubMed Google Scholar * Isao Hara View author publications

You can also search for this author inPubMed Google Scholar * Hiroshi Eto View author publications You can also search for this author inPubMed Google Scholar * Kazuo Gohji View author

publications You can also search for this author inPubMed Google Scholar * Soichi Arakawa View author publications You can also search for this author inPubMed Google Scholar * Sadao

Kamidono View author publications You can also search for this author inPubMed Google Scholar * Hideyuki Saya View author publications You can also search for this author inPubMed Google

Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Miyake, H., Hanada, N., Nakamura, H. _et al._ Overexpression of Bcl-2 in bladder cancer cells

inhibits apoptosis induced by cisplatin and adenoviral-mediated _P53_ gene transfer. _Oncogene_ 16, 933–943 (1998). https://doi.org/10.1038/sj.onc.1201602 Download citation * Received: 10

July 1997 * Revised: 26 September 1997 * Accepted: 26 September 1997 * Published: 03 March 1998 * Issue Date: 19 February 1998 * DOI: https://doi.org/10.1038/sj.onc.1201602 SHARE THIS

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Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * Bcl-2 * cisplatin * adenoviral-mediated _p53_ gene transfer * apoptosis * bladder cancer