青蒿琥酯诱导人胃癌细胞凋亡的分子机制研究

Molecular mechanisms of artesunate on human gastric cancer cell apoptosis

目的探讨青蒿琥酯对人胃癌HGC27细胞凋亡的影响及可能的分子机制。方法将HGC27细胞分为正常对照组、20 mg·L-1青蒿琥酯组、80 mg·L-1青蒿琥酯组、160 mg·L-1青蒿琥酯组,采用CCK8分别检测青蒿琥酯作用24、48和72 h后对HGC27细胞增殖的影响,流式细胞术检测青蒿琥酯对HGC27细胞凋亡的影响,Western blot检测青蒿琥酯对HGC27细胞中β-catenin、GSK-3β、c-Myc以及Caspase-3表达的影响。结果青蒿琥酯能抑制HGC27细胞增殖,与对照组相比,青蒿琥酯各浓度组的增殖抑制率显著升高(P<0.05),且具有浓度-时间依赖性。青蒿琥酯能诱导HGC27细胞凋亡,与对照组相比,青蒿琥酯各浓度组的细胞凋亡率显著升高(P<0.05),且具有浓度依赖性。Western blot检测发现青蒿琥酯能显著上调GSK-3β和Caspase-3的蛋白表达(P<0.05),抑制β-catenin和c-Myc的蛋白表达(P<0.05)。结论青蒿琥酯能明显抑制HGC27细胞的增殖,诱导细胞凋亡,这可能与其抑制Wnt/β-catenin信号通路活化有关。

Objective To discuss the effects and possible molecular mechanisms of artesunate on the cell apoptosis of human gastric cancer line HGC27.Methods The HGC27 cells were divided into the control group,artesunate groups at concentrations of 20 mg·L-1,80 mg·L-1 and 160 mg·L-1,respectively.The effects of artesunate on HGC27 cell proliferation were detected by CCK8 assay after treatment for 24 h,48 h and 72 h,respectively.The effects of artesunate on HGC27 cell apoptosis were detected by flow cytometry.The effects of artesunate on the expressions of β-catenin,glycogen synthase kinase-3β（GSK-3β）,c-Myc and cysteinyl aspartate specific proteinase-3（Caspase-3） were detected by Western blot.Results Artesunate could inhibit the HGC27 cell proliferation.Compared with the control group,the inhibitory rate of cell proliferation was significantly increased in artesunate groups at all concentrations（P〈0.05）,with a concentration-and timedependent manner.Artesunate could induce the HGC27 cell apoptosis.Compared with the control group,the rate of cell apoptosis was significantly increased in artesunate groups at all concentrations（P〈0.05）,with a concentration-dependent manner.The results of Western blot showed that the protein expression levels of GSK-3β and Caspase-3 were significantly up-regulated（P〈0.05）,while those of β-catenin and c-Myc were significantly down-regulated（P〈0.05） in artesunatetreated groups.Conclusion Artesunate can significantly inhibit the proliferation and induce the apoptosis of HGC27 cells,which may be related to inhibiting the activation of Wnt/β-catenin signaling pathway.