Effect of Histone Deacetylase Inhibitor TSA on Proliferation and Apoptosis of Human Hepatocellular Carcinoma Cell Line HepG2 and the Study of Its Mechanism

Objective To investigate the effect of TSA,an inhibitor specific for histone deacetylase,on the proliferation and apoptosis of human hepatocellular carcinoma cell line HepG2.Methods The cultured human hepatocellular carcinoma cells HepG2 were treated with different concentrations of TSA(5,50,250,500,1 000,2 000 nmol/L)for 24 hours.Then cell morphology was observed by the inverted light microscope and electron-microscopy,cell proliferation was detected using CCK-8 approach.Cell apoptosis rate of the control group (treated by the same amount of DMSO) and the group treated by 500 nmol/L TSA was determined using TUNEL approach.The expression of proliferation and apoptosis associated proteins of caspase-3,bax and bcl-2 were determined by immunocytochemistry approach.Results After treated with TSA,the proliferation of HepG2 cells reduced significantly,and HepG2 cells showed early apoptosis under electron-microscope.The proliferation activity of HepG2 cell in control group and different concentrations of TSA (5,50,250,500,1 000,2 000 nmol/L) group were (0.637±0.032),(0.552±0.016),(0.499±0.031),(0.393±0.007),(0.321±0.026),(0.277±0.010),(0.275±0.015),respectively,and the difference was significant(P0.01).Different concentrations of TSA inhibited the proliferation of HepG2 differently.After treated with 500 nmol/L TSA,apoptosis rate and the expressions of apoptosis-related protein caspase-3 and bax were significantly increased compared with the control group,but the level of bcl-2 did not change significantly (P0.05).Conclusion TSA can inhibit the proliferation of the hepatocarcinoma HepG2 cells through inducing cell apoptosis and increasing the expression of protein caspase-3 and bax.