Zhong Like
Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou 310022, China. *Corresponding author, E-mail:
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017 Sep;33(9):1212-1216.
Objective To investigate the mechanism of 18β-glycyrrhetinic acid (GA) piperazine derivative A30 on the antiproliferation of hepatocellular carcinoma SMMC-7721 cells in vitro. Methods The experiment included three groups: control group, 18β-GA group and A30 group. The proliferation activity was detected by MTT assay. Cell apoptosis and the change in the cycle of SMMC-7721 cells were evaluated by flow cytometry. Western blotting was used to observe the expressions of Bcl2 and caspase-8. Results The proliferation of SMMC-7721 cells was inhibited by A30 at the concentration of 2-128 μg/mL in a dose-dependent manner. 18β-GA and A30 could induce the apoptosis of SMMC-7721 cells, and the apoptosis rate of A30 group was significantly higher than that of the 18β-GA group. In the cell cycle analysis, the G2/M phase cells of 18β-GA and A30 groups increased remarkably as compared with the control group. A30 and 18β-GA could significantly enhance the expression of caspase-8, and decreased the expression of Bcl2. Conclusion The 18β-GA piperazine derivative A30 can inhibit the proliferation of SMMC-7721 cells in vitro, and the inhibitory effect is stronger than that of 18β-GA. The mechanism may be related to the inhibition of intracellular Bcl2 protein expression and the enhancement of caspase-8 expression.
目的 探讨18β-甘草次酸（GA）哌嗪衍生物A30体外对肝癌SMMC-7721细胞增殖的抑制作用机制。方法 实验分为三组：对照组、18β-GA组和A30组。采用MTT法检测细胞增殖活性。通过流式细胞术评估SMMC-7721细胞的凋亡及细胞周期变化。采用蛋白质免疫印迹法观察Bcl2和caspase-8的表达。结果 A30在2～128μg/mL浓度范围内可抑制SMMC-7721细胞增殖，呈剂量依赖性。18β-GA和A30均可诱导SMMC-7721细胞凋亡，且A30组凋亡率显著高于18β-GA组。细胞周期分析显示，18β-GA组和A30组G2/M期细胞较对照组明显增多。A30和18β-GA均可显著增强caspase-8的表达，降低Bcl2的表达。结论 18β-GA哌嗪衍生物A30可体外抑制SMMC-7721细胞增殖，且抑制作用强于18β-GA。其机制可能与抑制细胞内Bcl2蛋白表达及增强caspase-8表达有关。
