Ursolic acid combined with HDAC2 inhibitor inhibits proliferation of human hepatoma cell line HepG2

Abstract

Objective To investigate the effect of ursolic acid (UA) combined with HDAC2 inhibitor (SA) on the growth and proliferation of human hepatocarcinoma cell line HepG2 and its potential mechanism. Methods CCK-8, optical microscopy, cell clone formation and flow cytometry were used to evaluate the inhibitory effects of UA and SA on HepG2 cells after UA and SA monotherapy or combination therapy. Western blot was used to analyze the expression of HDAC2, AC-α-tubulin CDK2, CDK1, Bax, Bcl-2, and cleaved-PARP in the HepG2 cells after the treatment. Results UA had a significant inhibitory effect on the growth of HepG2 with a concentration and time-dependent manner (P＜0.01); UA inhibited HepG2 cell cloning, and the inhibitory effect was more significant when combined with SA (P＜0.01). UA combined with SA blocked HepG2 cell cycle at G1 phase (P＜0.01); HDAC2 was highly expressed in human hepatoma SMMC-7721, HepG2, and PLC5 cell lines, and UA combined with SA significantly down-regulated HDAC2, Bcl-2, CDK2 and cyclin E1 protein expression, while up-regulated the expression of AC-α-tubulin, Bax and cleaved-PARP. Conclusions The combined application of UA and SA has a synergistic inhibitory effect on the proliferation of HepG2 cells.

Keywords

• ursolic acid|liver cancer|histone deacetylase 2 (hdac2)|proliferation