Prognostic significance of Bcl-xL expression and efficacy of Bcl-xL targeting therapy in urothelial carcinoma

S. Yoshimine, Eiji Kikuchi, Takeo Kosaka, Shuji Mikami, A. Miyajima, Y. Okada, Mototsugu Oya

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Bcl-xL has an important role in the control of cell death through its inhibition of apoptosis. The aim of this study was to investigate the clinicopathological significance of Bcl-xL in upper urinary tract urothelial carcinoma (UTUC) and the therapeutic effect of targeting Bcl-xL protein in urothelial carcinoma (UC) cells. Methods: We evaluated the immunohistochemical expression of Bcl-xL in 175 UTUC patients to determine the clinical role of BclxL expression in clinical outcome. We used bafilomycin A1 (BMA) as a specific inhibitor of Bcl-xL to examine the biological effects in UC cells in vitro and in vivo. Results: Immunohistochemical analysis of Bcl-xL expression revealed that patients with a high Bcl-xL score had a significantly lower 5-year cancer-specific survival (CSS) rate (53.2%) than those with a low Bcl-xL score (77.2%) (P = 0.0011). Multivariate analysis indicated that a high Bcl-xL score was an independent prognostic factor of CSS (P = 0.023). BMA inhibited UMUC-3 cell proliferation in vitro by induction of apoptosis. Treatment with BMA significantly inhibited tumour growth in UMUC-3 tumours in this mouse xenograft model accompanied by an elevated apoptosis induction. Conclusion: Bcl-xL appears to be a significant molecular marker for the prognosis of UTUCs. Targeting Bcl-xL may be a promising therapeutic strategy for patients with UC.

Original languageEnglish
Pages (from-to)2312-2320
Number of pages9
JournalBritish Journal of Cancer
Volume108
Issue number11
DOIs
Publication statusPublished - 2013 Jun 11

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Carcinoma
Apoptosis
Urinary Tract
Neoplasms
Therapeutics
Therapeutic Uses
Heterografts
Cell Death
Multivariate Analysis
Survival Rate
Cell Proliferation
Survival
Growth
bafilomycin A1
Proteins
In Vitro Techniques

Keywords

  • Animal model
  • Bafilomycin
  • Bcl-xL
  • Prognostic factor
  • Upper urinary tract
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Prognostic significance of Bcl-xL expression and efficacy of Bcl-xL targeting therapy in urothelial carcinoma. / Yoshimine, S.; Kikuchi, Eiji; Kosaka, Takeo; Mikami, Shuji; Miyajima, A.; Okada, Y.; Oya, Mototsugu.

In: British Journal of Cancer, Vol. 108, No. 11, 11.06.2013, p. 2312-2320.

Research output: Contribution to journalArticle

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abstract = "Background: Bcl-xL has an important role in the control of cell death through its inhibition of apoptosis. The aim of this study was to investigate the clinicopathological significance of Bcl-xL in upper urinary tract urothelial carcinoma (UTUC) and the therapeutic effect of targeting Bcl-xL protein in urothelial carcinoma (UC) cells. Methods: We evaluated the immunohistochemical expression of Bcl-xL in 175 UTUC patients to determine the clinical role of BclxL expression in clinical outcome. We used bafilomycin A1 (BMA) as a specific inhibitor of Bcl-xL to examine the biological effects in UC cells in vitro and in vivo. Results: Immunohistochemical analysis of Bcl-xL expression revealed that patients with a high Bcl-xL score had a significantly lower 5-year cancer-specific survival (CSS) rate (53.2{\%}) than those with a low Bcl-xL score (77.2{\%}) (P = 0.0011). Multivariate analysis indicated that a high Bcl-xL score was an independent prognostic factor of CSS (P = 0.023). BMA inhibited UMUC-3 cell proliferation in vitro by induction of apoptosis. Treatment with BMA significantly inhibited tumour growth in UMUC-3 tumours in this mouse xenograft model accompanied by an elevated apoptosis induction. Conclusion: Bcl-xL appears to be a significant molecular marker for the prognosis of UTUCs. Targeting Bcl-xL may be a promising therapeutic strategy for patients with UC.",
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