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

Hideaki Miyake, Norihisa Hanada, Hideo Nakamura, Shunsuke Kagawa, Toshiyoshi Fujiwara, Isao Hara, Hiroshi Eto, Kazuo Gohji, Soichi Arakawa, Sadao Kamidono, Hideyuki Saya

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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.

Original languageEnglish
Pages (from-to)933-943
Number of pages11
JournalOncogene
Volume16
Issue number7
DOIs
Publication statusPublished - 1998 Feb 19
Externally publishedYes

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Keywords

  • Adenoviral-mediated p53 gene transfer
  • Apoptosis
  • Bcl-2
  • Bladder cancer
  • Cisplatin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Miyake, H., Hanada, N., Nakamura, H., Kagawa, S., Fujiwara, T., Hara, I., Eto, H., Gohji, K., Arakawa, S., Kamidono, S., & Saya, H. (1998). Overexpression of Bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer. Oncogene, 16(7), 933-943. https://doi.org/10.1038/sj.onc.1201602