Zhang Yun-Qi, Cai Yun, Liu Yuan, Zhao Bo-Xin, Li Guo-Feng
Department of Pharmacy, Nanfang Hospital/Rational Medication Evaluation and Drug Delivery Technology Lab, Nanfang Hospital/Guangdong Key Laboratory of New Drug Screening, School of Pharmaceutics, Southern Medical University, Guangzhou 510515, China. E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2018 Apr 20;38(4):477-482. doi: 10.3969/j.issn.1673-4254.2018.04.18.
To investigate the selective inhibitory effect of glycyrrhetinic acid on 4 hepatocellular carcinoma (HCC) cells with different proliferation rates and explore the underlying mechanisms.
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.
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 IC of 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.
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.
研究甘草次酸对4种增殖速率不同的肝癌（HCC）细胞的选择性抑制作用，并探讨其潜在机制。
采用MTT法检测4种肝癌细胞系，即SMMC - 7721、SK - HEP1、HEPG2和HEP3B的增殖速率。用甘草次酸（5、10、20、30、40和60 μmol/L）处理细胞后，采用MTT法分析细胞活力，并用蛋白质印迹法检测总ERK蛋白、p - ERK蛋白和拓扑异构酶IIα的表达。
在4种细胞系中，SMMC - 7721的增殖速率最低，SK - HEP1的增殖速率最高。甘草次酸处理48 h可剂量依赖性地抑制所有4种细胞系的体外增殖，对SMMC - 7721细胞的抑制作用最强，IC为28.04 μmol/L。细胞增殖速率与p - ERK和拓扑异构酶IIα的表达水平呈正相关，在SMMC - 7721细胞中最低，在SK - HEP1细胞中最高。50 μmol/L甘草次酸处理显著下调4种肝癌细胞系中p - ERK和拓扑异构酶IIα的表达（P<0.05），而25 μmol/L甘草次酸显著降低SMMC - 7721、HEPG2和HEP3B细胞中拓扑异构酶IIα和p - ERK的表达（P<0.05），但对SK - HEP1细胞无影响。
甘草次酸可抑制不同肝癌细胞的增殖，尤其是对增殖速率低的细胞。甘草次酸的抑制作用可能是通过降低拓扑异构酶IIα的表达和抑制ERK通路介导的。
