bafilomycin-a and Ureteral-Neoplasms

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.. 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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Animals; Apoptosis; bcl-X Protein; Female; Humans; Immunohistochemistry; Macrolides; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Molecular Targeted Therapy; Prognosis; Retrospective Studies; Ureteral Neoplasms; Xenograft Model Antitumor Assays