18β-甘草次酸哌嗪衍生物A30抑制SMMC-7721肝癌细胞增殖

18β-glycyrrhetinic acid piperazine derivative A30 inhibits the proliferation of SMMC-7721 hepatoma cells

目的研究18β-甘草次酸(18β-GA)哌嗪衍生物A30抑制肝癌SMMC-7721细胞增殖的机制。方法实验分为对照组、18β-GA组、A30组,采用MTT法检测SMMC-7721细胞增殖,流式细胞术检测SMMC-7721细胞凋亡和细胞周期,Western blot法检测胱天蛋白酶8(caspase-8)和Bcl2蛋白水平。结果 (2~128)μg/m L A30均可抑制SMMC-7721细胞的增殖,呈剂量依赖性。18β-GA和A30均可诱导SMMC-7721细胞凋亡,并且A30处理细胞的凋亡率显著高于18β-GA组。与对照组相比,18β-GA和A30组的G2/M期细胞显著增加,caspase-8蛋白水平均显著升高,而Bcl2水平均显著降低。结论 A30能抑制SMMC-7721细胞增殖,抑制效果强于18β-GA,与降低细胞Bcl2水平和增加caspase-8水平有关。

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 cel s was inhibited by A30 at the concentration of2-128 μg/m L in a dose-dependent manner. 18β-GA and A30 could induce the apoptosis of SMMC-7721 cel s,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 of18β-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.