积雪草酸对人胃癌细胞增殖、迁移和侵袭的影响

Effect of Asiatic Acid on Proliferation,Migration and Invasion of Human Gastric Cancer Cells

目的探讨积雪草酸(asiatic acid,AA)对人胃癌细胞增殖、迁移和侵袭的影响及其分子机制。方法将人胃癌细胞培养后使用不同浓度的(0、10、20、30μmol·L^-1)积雪草酸对其进行处理。采用结晶紫染色和克隆形成实验、划痕实验、Transwell实验分别检测各浓度积雪草酸处理的人胃癌细胞增殖、迁移、侵袭情况;采用Western blot检测各浓度积雪草酸处理的人胃癌细胞上皮-间质转化和基质金属蛋白酶的表达情况及Wnt/β-catenin信号和PI3K/AKT信号的活化情况。结果积雪草酸能够抑制人胃癌细胞的增殖(P<0.01)、迁移(P<0.01)和侵袭(P<0.01),能够抑制人胃癌细胞上皮间质-转化和基质金属蛋白酶表达(P<0.01)。积雪草酸可抑制Wnt/β-catenin信号,降低β-catenin及其下游靶分子Cyclin D1和c-Myc的蛋白水平;可抑制PI3K/AKT信号,导致AKT在308位苏氨酸和473位丝氨酸磷酸化水平降低。结论积雪草酸可抑制人胃癌细胞的增殖、迁移和侵袭,这可能与其对Wnt/β-catenin和PI3K/AKT信号的抑制作用有关。

Objective To investigate the effect of asiatic acid(AA)on proliferation,migration and invasion of human gastric cancer cells and its possible mechanism of action.Methods Human gastric cancer cells were treated with different concentrations of AA(0,10,20 and 30μmol·L^-1).Cell proliferation was determined by crystal violet staining and colony formation assay.Cell migration was analyzed by wound healing assay.Cell invasion was tested by transwell assay.Epithelial-mesenchymal transition(EMT),matrix metalloproteinase(MMP)expression and activation of Wnt/β-catenin and PI3K/AKT signaling were detected by Western blot.Results AA treatment inhibited the proliferation,migration and invasion and decreased EMT and MMP expression in human gastric cancer cells(all P<0.01).Furthermore,AA inactivated Wnt/β-catenin signaling through reducing the protein levels ofβ-catenin and its downstream target molecules Cyclin D1 and c-Myc.Moreover,AA blocked PI3K/AKT signaling by suppressing the phosphorylation of PI3K/AKT at Thr308 and Ser473.Conclusion AA treatment can inhibit the proliferation,migration and invasion of human gastric cancer cells possibly through suppression of Wnt/β-catenin and PI3K/AKT signaling.