Gallbladder carcinoma (GBC), an aggressive and mostly lethal malignancy, is known to be resistant to a number of apoplotic stimuli. Here, we report for the first time the pro-apoptosis role of arsenic trioxide (AS(2)O(3)) in gallbladder carcinoma and identify the contribution of Bcl-2 in the AS(2)O(3)-induced apoptosis. The treatment of AS(2)O(3) in gallbladder carcinoma cells could induce apoptosis in a dose-dependent manner and downregulate the expression of anti-apoptotic protein Bcl-2 at mRNA level. Moreover, Bcl-2 overexpression could protect gallbladder carcinoma cells from As2O3-induced apoptosis, indicating the contribution of Bcl-2 in AS(2)O(3)-induced apoptosis. Taken together, these results suggest that arsenic trioxide induces gallbladder carcinoma cell apoptosis via downregulation of Bcl-2, which may have important therapeutic implications in gallbladder carcinoma patients. (c) 2006 Elsevier Inc. All rights reserved.