Apoptosis of Human Cholangiocarcinoma Cell Lines induced by β-Escin through Mitochondrial Caspase-dependent Pathway

作者：Shen, Dong-Yan; Kang, Jin-He; Song, Wei; Zhang, Wen-Qing; Li, Wen-Gang; Zhao, Yan; Chen, Qing-Xi^*

来源：Phytotherapy Research, 2011, 25(10): 1519-1526.

DOI：10.1002/ptr.3435

• cholangiocarcinoma
• beta-escin
• caspase-3
• bcl-2
• bax
• reactive oxygen species

The study aimed to evaluate the effects of beta-escin on human cholangiocarcinoma cell lines (QBC939, Sk-ChA-1 and MZ-ChA-1) and to explore its mechanisms. Cell growth, cell cycle and apoptosis were investigated, respectively, by MTT assay, single PI and FITC/PI double-staining flow cytometry, and fluorescence microscopy. The protein expression was determined by western blotting. The study revealed that beta-escin inhibited cholangiocarcinoma cell growth in a dose- and time-dependent manner, and the cell cycle of QBC939 and Sk-ChA-1 cells was arrested in the G2/M phase, and MZ-ChA-1 cells in G1 phase. Apoptosis of the three cholangiocarcinoma cell lines induced by beta-escin was associated with the collapse of the mitochondrial membrane potential and the activation of caspase-3. The apoptotic effect of beta-escin was suppressed by pancaspase inhibitor z-VAD-fmk. Molecular dissection revealed that the antiapoptotic protein bcl-2 was down-regulated after cholangiocarcinoma cell lines were treated with beta-escin, while the protein levels of bax and p53 were unchanged. Apoptosis was accompanied by an increase in reactive oxygen species (ROS). These results suggest that beta-escin induces apoptosis of cholangiocarcinoma cells through an intrinsic mitochondrial caspase-dependent pathway, and the increase in the bax/bcl-2 ratio and ROS may play important roles in beta-escin-induced apoptosis of cholangiocarcinoma cells.

• 出版日期2011-10
• 单位厦门大学