尪五味子乙素通过PI3K/Akt信号通路调控内质网应激促进胃癌细胞凋亡

Schisandra B regulates endoplasmic reticulum stress and promotes gastric cancer cell apoptosis through PI3K/Akt signaling pathway

目的探讨五味子乙素(Sch B)对胃癌BGC-823细胞凋亡的影响及可能机制。方法采用CCK-8法检测不同浓度Sch B对BGC-823细胞的抑制作用。根据不同的处理方式将细胞分为空白对照组、Sch B组、SC-79(Akt激活剂)组和Sch B+SC-79组,流式细胞仪检测各组细胞的凋亡情况;Western blot检测Bcl-2相关X蛋白(BAX)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、C/EBP同源蛋白(CHOP)、胰腺内质网激酶(PERK)、真核细胞起始因子2α(EIF-2α)、p-PERK、p-EIF-2α和转录激活因子4(ATF4)、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)和pAkt蛋白表达。结果Sch B干预后可显著降低BGC-823胃癌细胞存活率,促进细胞凋亡,上调Bax和Caspase-3的表达;促进内质网应激相关蛋白CHOP、p-PERK、p-EIF-2α、ATF4表达,抑制p-PI3K和p-Akt表达;给予Akt激活剂SC-79和Sch B后,SC-79对Sch B引起的BGC-823胃癌细胞凋亡及内质网应激水平增强具有回复作用。结论Sch B可能通过抑制PI3K/Akt信号通路引发内质网应激促进BGC-823胃癌细胞凋亡。

Objective To investigate the effect of Schisandra B(Sch B)on apoptosis of gastric cancer BGC-823 cells and its possible mechanism.Methods The inhibitory effect of Sch B on BGC-823 cells was detected by CCK-8assay.Cells were divided into blank control group,Sch group,SC-79(Akt activator)group and Sch B+SC-79 group according to different treatment methods.Flow cytometry was used to detect apoptosis of cells in each group.Western blot was used to detect the expressions of Bcl-2 associated X protein(BAX),cysteine aspartic protease-3(Caspase-3),C/EBP homologous protein(CHOP),pancreatic endoplasmic reticulum kinase(PERK),eukaryotic initiation factor 2α(EIF-2α),p-PERK,pEIF-2αand transcriptional activator 4(ATF4),phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)and p-Akt.Results Sch B significantly decreased the survival rate of BGC-823 gastric cancer cells,promoted apoptosis of BGC-823 gastric cancer cells,up-regulated the expressions of Bax and Caspase-3,promoted the expressions of CHOP,p-PERK,PIF-2α,ATF4,and inhibit the expressions of p-PI3K and p-Akt.After the administration of Akt activators SC-79 and Sch B,SC-79 had a recovery effect on the apoptosis of BGC-823 gastric cancer cells and the enhancement of endoplasmic reticulum stress level induced by Sch B.Conclusion Sch B can induce endoplasmic reticulum stress to promote BGC-823 gastric cancer cell apoptosis by inhibiting PI3K/Akt signaling pathway.