槲皮素通过PI3K/AKT信号通路抑制奥沙利铂耐药胃癌细胞迁移

Quercetin inhibits the migration of oxaliplatin-resistant gastric cancer cells through the PI3K/AKT signaling pathway

目的探讨槲皮素抑制奥沙利铂耐药胃癌细胞(SGC-7901/L-OHP)迁移的作用及其可能机制。方法培养人胃癌敏感细胞(SGC-7901)和SGC-7901/L-OHP,槲皮素处理SGC-7901和SGC-7901/L-OHP细胞,通过CCK8检测槲皮素对其增殖的影响;采用划痕和Transwell实验检测SGC-7901和SGC-7901/L-OHP细胞迁移能力,以及槲皮素对SGC-7901/L-OHP细胞迁移能力的作用;采用Western blot检测槲皮素对SGC-7901/L-OHP细胞p-PI3K、p-AKT、MMP2和MMP9蛋白表达的作用;采用PI3K激活剂(IGF-1)和槲皮素联合处理SGC-7901/L-OHP细胞,观察其对SGC-7901/L-OHP细胞迁移能力以及对p-PI3K、p-AKT、MMP2和MMP9蛋白表达的影响。结果划痕和Transwell实验结果显示,耐药细胞的迁移能力明显强于敏感细胞(P<0.05),槲皮素能够抑制SGC-7901/L-OHP细胞的迁移能力(P<0.05)。Western blot结果显示,槲皮素能抑制p-PI3K、p-AKT、MMP2和MMP9的表达(P<0.05)。与槲皮素组比较,IGF-1与槲皮素联合处理促进SGC-7901/L-OHP细胞迁移(P<0.05),促进p-PI3K、p-AKT、MMP2和MMP9蛋白表达(P<0.05)。结论槲皮素可能通过抑制PI3K/AKT信号通路抑制胃癌奥沙利铂耐药细胞SGC-7901/L-OHP细胞迁移。

Objective To investigate the effect of quercetin on the migration of oxaliplatin-resistant gastric cancer cells(SGC-7901/L-OHP)and its possible mechanism.Methods Human gastric cancer sensitive cells(SGC-7901)and SGC-7901/L-OHP were cultured.SGC-7901/L-OHP cells were treated with quercetin,and the effect of quercetin on their proliferation was detected by CCK8;the effect of quercetin on the migration ability of SGC-7901/L-OHP cells was detected by scratch and transwell experiments;the effect of quercetin on the expression of p-PI3K,p-AKT,MMP2,and MMP9 proteins in SGC-7901/L-OHP cells was detected by western blot;after treating SGC-7901/L-OHP cells with a combination of PI3K activator(IGF-1)and quercetin,the effects on the migration ability of SGC-7901 cells and the expression of p-PI3K,p-AKT,MMP2,and MMP9 proteins were observed.Results Scratch and transwell experiments showed that the migration ability of drug-resistant cells was significantly stronger than that of sensitive cells(P<0.05),and quercetin could inhibit the migration ability of SGC-7901/L-OHP cells(P<0.05).Western blot showed that quercetin could inhibit the expression of p-PI3K,p-AKT,MMP2,and MMP9(P<0.05).Compared with the quercetin group,the combined treatment with IGF-1 and quercetin promoted the migration of SGC-7901/L-OHP cells and the expression of p-PI3K,p-AKT,MMP2 and MMP9 proteins(P<0.05).Conclusion Quercetin may inhibit the migration of oxaliplatin-resistant SGC-7901/L-OHP cells in gastric cancer by inhibiting the PI3K/AKT signaling pathway.