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

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 Bcl-xL 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.

• Authors: S Yoshimine, E Kikuchi, T Kosaka, S Mikami, A Miyajima, Y Okada, M Oya
• Journal: British journal of cancer (Br J Cancer) Vol. 108 Issue 11 Pg. 2312-20 (Jun 11 2013) ISSN: 1532-1827 [Electronic] England
• PMID: 23674090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCL2L1 protein, human
• Macrolides
• bcl-X Protein
• bafilomycin A

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Apoptosis (drug effects)
• Female
• Humans
• Immunohistochemistry
• Macrolides (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Molecular Targeted Therapy
• Prognosis
• Retrospective Studies
• Ureteral Neoplasms (drug therapy, metabolism, pathology)
• Xenograft Model Antitumor Assays
• bcl-X Protein (antagonists & inhibitors, biosynthesis)