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.
Written by:
Yoshimine S, Kikuchi E, Kosaka T, Mikami S, Miyajima A, Okada Y, Oya M. Are you the author?
Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Reference: Br J Cancer. 2013 May 14. Epub ahead of print.
doi: 10.1038/bjc.2013.216
PubMed Abstract
PMID: 23674090
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