18β-甘草次酸抑制肝癌细胞生长的实验研究
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王效民, Email: zhoucszhoujia@126.com

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重大传染病防治重大科技专项基金资助项目(2008ZX 10002-019)。


Experimental study of 18β-glycyrrhetinic acid inhibiting growth of hepatocellular carcinoma cells
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    摘要:

    目的:探讨18β-甘草次酸(GA)对肝癌细胞生长的影响。 方法:用不同浓度的GA或阿霉素(ADM)处理肝癌细胞(Hepa1-6)及正常肝细胞(AML-12)不同时间后,分析细胞的抑制情况及半数抑制浓度(IC50);根据IC50,选择合适浓度的GA处理Hepa1-6细胞一定时间后,检测细胞的凋亡情况。 结果:低浓度GA对两种细胞增殖均无明显影响,当GA浓度>8 μg/mL时,对两种细胞的增殖均有明显的抑制作用,且抑制作用随药物浓度升高、作用时间延长而增加;ADM所有浓度对两种细胞的增殖均有抑制作用,且抑制作用随浓度升高而增加,但随时间延长而减弱。GA对Hepa1-6细胞的IC50低于对AML-12细胞的IC50,当药物作用48 h时,GA对两种细胞的IC50的差值最大,而ADM对Hepa1-6细胞的IC50在任何时间都高于对AML-12细胞的IC50;选择25 μg/mL的GA处理Hepa1-6细胞48 h(该条件下,Hepa1-6细胞的增殖抑制率为50%,而AML-12细胞的增殖抑制率为3.8%),Hepa1-6细胞的明显增加,且主要是早期凋亡(P<0.05)。 结论:GA能够抑制肝癌的生长,其机制可能与诱导肝癌细胞凋亡有关;在治疗肝癌方面,GA可能较ADM更为安全,毒副作用更小。

    Abstract:

    Objective: To investigate the effect of 18β-glycyrrhetinic acid (GA) on growth of hepatocellular carcinoma cells. Methods: The hepatocellular carcinoma cells (Hepa1-6) and normal hepatic cells (AML-12) were exposed to different concentrations of GA or adriamycin (ADM) for different time periods, after that, the cell growth inhibition and half inhibitory concentration (IC50) were analyzed. Then, after Hepa1-6 cells were treated with GA of an appropriate concentration selected according to IC50 for a certain time period, the cell apoptosis was measured. Results: Low concentrations of GA exerted no obvious inhibitory effects on proliferations of the two types of cells, but had remarkable inhibitory effects on proliferations of them at the concentrations >8 μg/mL, and the effects were increased with the elevation of the GA concentration and time prolongation. All concentrations of ADM showed evident inhibitory effects on proliferations of the two types of cells, and these effects were increased with the rising of the ADM concentration but decreased as time elapsed. The IC50 of GA for Hepa1-6 cells was lower than that for AML-12 cells, and the IC50 difference between them reached a largest value at 48 h treatment, while the IC50 of ADM for Hepa1-6 cells was higher than that for AML-12 cells at any time period of treatment. After treatment with 25 μg/mL GA for 48 h (under this condition, the inhibition rate of proliferation in Hepa1-6 cells was 50%, while in AML-12 cells was only 3.8%), the apoptosis in Hepa1-6 cells was significantly increased, which mainly resulted from early apoptosis (P<0.05). Conclusion: GA can inhibit the growth of hepatocellular carcinoma cells and the mechanism may be related to its inducing cells apoptosis. GA may be safer and has less toxic side effects for treatment of hepatocellular carcinoma.

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周长升|芶欣|王效民|黄建钊.18β-甘草次酸抑制肝癌细胞生长的实验研究[J].中国普通外科杂志,2016,25(8):1168-1174.
DOI:10.3978/j. issn.1005-6947.2016.08.014

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  • 收稿日期:2016-05-30
  • 最后修改日期:2016-07-08
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  • 在线发布日期: 2016-08-15