首页> 中文期刊> 《中国病理生理杂志》 >GSTP1上调对奥沙利铂诱导人肝癌细胞株HepG2凋亡的影响

GSTP1上调对奥沙利铂诱导人肝癌细胞株HepG2凋亡的影响

         

摘要

AIM: To investigate the effect of GSTP1 over-expression on the sensitivity of human hepatoma HepG2 cells to oxaliplatin (OXA).METHODS: Adenovirus carrying GSTP1 (Ad-GSTP1) was used to infect HepG2 cells for establishing the cell line over-expressing GSTP1.The cells were randomly divided into 6 groups: control, vehicle, Ad-GSTP1, OXA, OXA +vehicle and OXA +Ad-GSTP1.The cell survival rates were examined by CCK-8 assay, and the apoptotic rates were analyzed by flow cytometry.The protein levels of GSTP1, Akt, mTOR, p-Akt and p-mTOR were deter-mined by Western blot.RESULTS: OXA decreased the cell survival rate in a dose-dependent manner (P <0.05).The protein expression of GSTP1 increased after transfection with adenovirus.At basal level, up-regulation of GSTP1 signifi-cantly decreased the cell survival rate, increased the cell apoptosis, and inhibited the phosphorylation levels of Akt and mTOR (P <0.05).Moreover, GSTP1 over-expression enhanced the effect of OXA on the cell viability, cell apoptosis, and further inhibited the phosphorylation levels of Akt and mTOR ( P <0.05).CONCLUSION: Over-expression of GSTP1 augments the enhanced effect of OXA on HepG2 cell apoptosis, which may be related to the inactivation of Akt/mTOR signaling pathway.%目的:探讨过表达 GSTP1后 HepG2细胞对奥沙利铂(oxaliplatin,OXA)敏感性的影响及其相关机制。方法:采用腺病毒载体转染人肝癌细胞株 HepG2,获得过表达 GSTP1的 HepG2细胞;实验分为空白对照组(control 组)、载体组(vehicle 组)、过表达 GSTP1组(Ad-GSTP1组)、OXA 组、OXA +vehicle 组和 Ad-GSTP1+OXA组;MTT 法和流式细胞术检测 HepG2细胞的存活率和凋亡率;Western blot 法检测 HepG2细胞中 GSTP1、Akt、mTOR、p-Akt 和 p-mTOR 的蛋白水平。结果: OXA 剂量依赖性地降低 HepG2细胞的存活率(P <0.05);腺病毒转染后 HepG2细胞的 GSTP1蛋白表达增加;基础状态下,过表达 GSTP1可降低 HepG2细胞的存活率,促进细胞凋亡,抑制 Akt 和 mTOR 磷酸化水平(P <0.05);给予 OXA 处理后,上调 GSTP1表达增强了 OXA 降低 HepG2细胞存活率的作用,凋亡率进一步增加,Akt 和 mTOR 蛋白的磷酸化水平进一步下降,与加药组相比差异有统计学显著性(P <0.05)。结论:上调 GSTP1表达可增强 OXA 促进 HepG2细胞凋亡的作用,其机制可能与 Akt/mTOR 通路有关。

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