Glycyrrhetinic acid selectively inhibits proliferation of hepatocellular carcinoma cells in vitro

ZHANG Yunqi; CAI Yun; LIU Yuan; ZHAO Boxin; LI Guofeng

doi:10.3969/j.issn.1673-4254.2018.04.18

Abstract：Objective To investigate the selective inhibitory effect of glycyrrhetinic acid on 4 hepatocellular carcinoma (HCC) cells with different proliferation rates and explore the underlying mechanisms.Methods MTT method was used to detect the proliferation rates of 4 HCC cell lines, namely SMMC-7721, SK-HEP1, HEPG2 and HEP3B. Following treatment of the cells with glycyrrhetinic acid(5,10,20,30,40,and 60 μmol/L),the cell viability was analyzed using MTT assay and the expressions of total ERK protein, p-ERK protein and topoisomerase IIα were detected using Western blotting. Results Among the 4 cell lines,SMMC-7721 had the lowest and SK-HEP1 had the highest proliferation rate.Treatment with glycyrrhetinic acid for 48 h dose-dependently inhibited the proliferation of all the 4 cell lines in vitro and produced the strongest inhibitory effect in SMMC-7721 cells with the IC50of 28.04 μmol/L.The proliferation rate of the cells was positively correlated with the expression levels of p-ERK and topoisomerase IIα, which were the lowest in SMMC-7721 cells and the highest in SK-HEP1 cells. Treatment with 50 μmol/L glycyrrhetinic acid significantly down-regulated the expressions of p-ERK and topoisomerase IIα in the 4 HCC cell lines (P<0.05), while 25 μmol/L glycyrrhetinic acid significantly reduced the expression of topoisomerase IIα and p-ERK in SMMC-7721, HEPG2 and HEP3B cells (P<0.05) but not in SK-HEP1 cells. Conclusion Glycyrrhetinic acid can inhibit the proliferation of different HCC cells particularly in cells with a low proliferation rate. The inhibitory effect of glycyrrhetinic acid might be mediated by reducing the expressions of topoisomerase IIα and inhibiting the ERK pathway.