Anticancer effect of arsenic trioxide on cholangiocarcinoma: in vitro experiments and in vivo xenograft mouse model

The purpose of our study was to investigate anticancer activity of arsenic trioxide (As₂O₃) on cholangiocarcinoma through in vitro and in vivo experiments using human cholangiocarcinoma cancer cells (CC-t6 cells) and a nude mouse model. The effect of As₂O₃ on CC-t6 cell survival was determined in vitro using MTT assay. Analysis of cell cycle phase distribution and quantification of apoptosis/necrosis, which were achieved by flow cytometry, were performed in order to understand the mechanism of As₂O_3. In vivo experiment was performed to assess the effectiveness of local injection of As₂O₃ on tumor inhibition by comparing the following three groups each consisting of five nude mouse xenograft models: high dose As₂O₃ (5 mg/kg), low dose As₂O₃ (1 mg/kg), and saline. In MTT assay, As₂O₃ inhibited the growth of CC-t6 cells more effectively than cisplatin or adriamycin at concentrations between 1 and 100 μM for most time points between 24 and 72 h (p < 0.05). With increased concentration of As₂O₃, there was dose-dependent increase in G ₀/G ₁ phase and dose-dependent decrease in S phase. As₂O₃-mediated inhibition of cell viability was achieved via induction of apoptosis and necrosis in a dose-dependent manner. Injection of As₂O₃ into CC-t6-induced tumors in nude mice inhibited the growth of subcutaneous tumor xenografts. As₂O₃ treatment dose-dependently inhibited the proliferation of CC-t6 cells via G ₀/G ₁ phase arrest and retarded tumor growth in nude mice, suggesting that As₂O₃ may be effective in the treatment of cholangiocarcinoma.