Effect of sodium valproate on inhibiting the growth of human cholangiocarcinoma cells and its mechanism

Abstract

Objective To investigate the effect and mechanism of sodium valproate on inhibiting the growth of human cholangiocarcinoma cells. Methods Human cholangiocarcinoma TFK-1 cells were respectively treated with 0.5, 1.0, 2.0, 4.0 and 8.0 mmol/L of sodium valproate for 1, 3 and 5 d. And the control and blank groups were also established. The inhibitory effect of sodium valproate on the growth of human cholangiocarcinoma cells was detected by cell counting kit (CCK)-8 assay. The effect of sodium valproate on the cell apoptosis rate and cell cycle was detected by flow cytometry. The nude mice subcutaneous implantation tumor models of TFK-1 cells was established and the experimental and control groups were assigned to observe the effect of sodium valproate on the growth of tumor. The experiment data in two groups were compared using t test, and the multi-group comparison was conducted using one way analysis of variance and LSD-t test. Results The inhibitory effect of sodium valproate on the growth of human cholangiocarcinoma TFK-1 cells was observed in a dose- and time-dependent manner. As the concentration of sodium valproate increased, the cell apoptosis rate and the percentage of cells in the G2/M phase significantly increased. Compared with (8.6±2.3)% in the control group, the cell apoptosis rate (57.5±6.2)% in the 8.0 mmol/L experimental group significantly increased at 3 d. Compared with (12.0±2.6)% in the control group, the percentage of cells in the G2/M phase (42.5±5.4)% in the 8.0 mmol/L experimental group significantly increased (LSD-t=17.557, 12.465; P<0.05). At 31 d after the first treatment, the tumor volume (338±11) mm3 in the 8.0 mmol/L experimental group significantly decresed, compared with (426±14) mm3 in the control group (t=-15.630, P<0.05). Conclusions Sodium valproate can significantly inhibit the growth of human cholangiocarcinoma cells, and its mechanisms include cell cycle arrest and cell apoptosis. Key words: Sodium valproate; Bile duct neoplasms; Cell cycle; Apoptosis; Neoplasm seeding; Mice