薯蓣皂苷通过逆转上皮间质转化抑制高糖诱导的肺癌细胞转移机制

Mechanism of Dioscin in inhibiting hyperglycemia-induced lung cancer cells metastasis through reversing EMT

目的:探讨薯蓣皂苷(Dioscin)对高糖诱导的肺癌A549细胞增殖、侵袭迁移的抑制作用以及其对上皮间质转化(EMT)的影响。方法:将A549细胞用高糖及不同浓度的Dioscin(0、0.5、1、2、4、8μmol/L)处理后,分别采用四甲基偶氮唑盐(MTT)法检测细胞活力;划痕愈合实验和Transwell小室实验检测细胞的迁移能力和侵袭能力;Western blot检测EMT相关蛋白E-cadherin和Vimentin的表达情况。结果:高糖促进A549细胞增殖,且具有浓度和时间依赖性,而Dioscin可抑制A549细胞的生长,其24 h的IC_(50)为10.04μmol/L。划痕愈合实验和Transwell小室实验结果显示,高糖显著促进A549细胞的迁移和侵袭能力(P<0.01),Dioscin则能显著抑制高糖诱导的细胞迁移和侵袭能力(P<0.01)。Western blot法检测结果显示,高糖可改变EMT相关蛋白的表达水平,使细胞中E-cadherin蛋白表达下降、Vimentin蛋白表达升高(P<0.01),Dioscin则可逆转高糖诱导的变化(P<0.01)。结论:Dioscin可抑制高糖诱导的肺癌A549细胞增殖、迁移和侵袭,同时对高糖诱导的肺癌A549细胞EMT进程也具有一定的抑制作用。

Objective: To investigate the effects of Dioscin on cell proliferation, invasion, migration and epithelialmesenchymal transition(EMT) in high glucose-induced lung cancer A549 cells. Methods: The effects of high glucose and Dioscin(0, 0.5, 1, 2, 4, 8 μmol/L) on the viability of A549 cells were measured by MTT assay. The ability of cell migration was measured by scratch healing assay. The cell invasion ability was analyzed by Transwell method. The protein expression of E-cadherin and Vimentin in the A549 cells were detected by Western blot. Results: High glucose could increase the proliferation rate of A549cells. Then, the cell activity of the A549 cells was significantly inhibited by Dioscin in a dose-time dependent manner. IC_(50) of Dioscin(24 h) for the A549 cells was 10.04 μmol/L. The results of scratch healing assay and Transwell method showed that high glucose significantly promoted the migration and invasion of A549 cells(P<0.01), while Dioscin significantly inhibited the migration and invasion of A549 cells induced by high glucose(P<0.01). Western blot showed that high glucose could change the expression level of EMT related proteins, reduce the expression of E-cadherin protein and increase the expression of Vimentin protein in cells(P<0.01), and Dioscin could reverse the changes induced by high glucose(P<0.01). Conclusion: Dioscin could suppress the effect of high glucose-induced cell proliferation, invasion and migration in lung cancer A549 cells. Moreover, Dioscin could also reverse high glucose-induced EMT in lung cancer A549 cells.