人参皂苷Rg5对胃癌细胞周期和侵袭的影响及其机制

目的:观察ginsenoside-Rg5 (Rg5) 对胃癌细胞周期和侵袭的影响,并探讨其机制。方法:采用不同浓度人参皂苷ginsenoside-Rg3 (Rg3)和Rg5 (10、20、30、40、50 μmol/L) 处理人正常胃粘膜细胞GES-1和胃癌细胞株AGS、MKN-45 24 h,每个浓度设3个复孔。通过CCK-8检测细胞存活率。通过流式细胞仪检测细胞周期、Transwell小室分析迁移和免疫印迹法及ELISA法检测相关蛋白。结果:CCK8 实验结果显示人参皂苷Rg3和Rg5 对GES-1细胞无毒副作用,但可以抑制胃癌细胞AGS和MKN-45的增值。且Rg5抗胃癌细胞的活性强于Rg3。 20 μmol/L Rg5诱导MKN-45细胞发生S期阻滞通过降低CyclinA1/CDK2/PCNA 的表达和升高P21^CIPI蛋白表达。Rg5还可以抑制MKN-45癌细胞的迁移通过降低MMP2和MMP9的表达。WB结果显示Rg5抑制胃癌增殖及迁移主要是通过抑制Notch1蛋白的表达从而调控其下游的周期及侵袭相关蛋白。结论:Rg5抗胃癌细胞活性高于Rg3且通过调控Notch1通路抑制细胞增殖和迁移。

Effects of ginsenoside Rg5 on cell cycle and invasion of gastric cancer

Objective:To investigate the effects of ginsenoside Rg5 on the proliferation,cycle and invasion of gastric carcinoma cell lines,providing experimental evidence for the anti-tumor mechanism of ginsenoside Rg5.Methods:In this experimental study,the human immortalized normal gastric mucosa cell GES-1 and gastric adenocarcinoma cell lines AGS and MKN-45 were treated with Rg3 and Rg5 at the concentrations of 10,20,30,40 and 50μmol/L for 24 h,3 parallel holes were set for each group.A cell viability test,cell cycle analysis,transwell assay,ELISA and immunoblotting were performed.Results:The viabilities of AGS and MKN-45 were suppressed by Rg3 and Rg5 in a concentration-dependent manner.The activity of Rg5 against gastric cancer cells was stronger than that of Rg3,and its toxicity to GES-1 was lower than that of Rg3.After the treatment of 20μmol/L of Rg5 for 24 h,Rg5 could generate cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2(CDK2)/proliferating cell nuclear antigen(PCNA)complex production and increasing the P21 CIPI.Rg5 inhibited the migration of MNK-45 cells by reducing the expressions of MMP2 and MMP9.WB results showed that Rg5 inhibited the proliferation and migration of gastric cancer mainly by inhibiting the expression of Notch1 protein to regulate its downstream cycle and invasion related proteins.Conclusion:These results suggest that Rg5 exhibits stronger anti-cancer activity than Rg3 in gastric cancer cells,and has higher anti-gastric cancer cell activity than Rg3 and inhibits cell proliferation and migration by regulating the Notch1 pathway.