GRP78在肝癌细胞抵抗棕榈酸诱导凋亡中的作用  

The roles of GRP78 in inhibiting PA-mediated hepatocellular carcinoma cells apoptosis

作　　者：王进举[1] 张春燕[2] 肖斌[2] 李洪[2] 敬健雄 冯春红[1] 夏先明[1] 代荣阳[2] 

机构地区：[1]泸州医学院附属医院肝胆外科,四川泸州646000 [2]泸州医学院生物化学教研室

出　　处：《中国老年学杂志》2016年第9期2056-2059,共4页Chinese Journal of Gerontology

基　　金：国家自然科学基金项目(No.81472312);教育部新世纪优秀人才支持计划(No.NCET-11-1058);四川省科技厅-泸州市-泸州医学院联合基金(No.14JC0082;14ZC0070;14JC0038);泸州市-泸州医学院联合基金(No.2013LZLY-J06);四川省杰出青年学术技术带头人培育计划(No.2013JQ0045)

摘　　要：目的探讨内质网应激(ER stress)信号调控对棕榈酸(PA)诱导肝癌细胞凋亡的影响及其机制。方法培养人肝癌细胞SMMC-7721,在采用ER stress抑制剂4-苯丁酸(PBA)和过表达葡萄糖调节蛋白(GRP)78的基础上,利用流式细胞和免疫印迹技术分析ER stress以及GRP78对PA诱导肝癌细胞凋亡的影响。结果 PA诱导肝癌细胞发生ER stress,PBA抑制ER stress并减弱了PA诱导的肝癌细胞凋亡(P<0.05)。PA和ER stress诱导剂衣霉素(Tun)对ER stress分子标志的诱导水平差异显著(P<0.05),其中PA诱导的GRP78远低于Tun的诱导作用。过表达GRP78明显抑制了PA诱导的肝癌细胞凋亡(P<0.05)。结论 GRP78的诱导表达不足在PA介导的肝癌细胞凋亡中起重要作用。Objective To investigate the effects and mechanisms of endoplasmic reticulum stress on PA-induced apoptosis in human hepatocellular carcinoma cells. Methods Endoplasmic reticulum stress inhibitor PBA was used to decrease endoplasmic reticulum stress,and glucose-regulated protein（ GRP） 78 expression vectors were used to increase the protein level of GRP78 in SMMC-7721 cells in response to PA. The effects of endoplasmic reticulum stress and GRP78 on PA-induced SMMC-7721 cells apoptosis were analyzed by flow cytometry and Western blot analysis. Results PA treatment resulted in the activation of endoplasmic reticulum stress. Importantly,PBA pre-treatment obviously decreased PA-mediated apoptosis in SMMC-7721 cells. The pattern of PA-initiated endoplasmic reticulum stress was different from endoplasmic reticulum inducer tunicamycin-induced endoplasmic reticulum stress. GRP78 protein level induced by PA was much lower than that of tunicamycin in SMMC-7721 cells. GRP78 expression vectors transient transfection inhibited PA-induced apoptosis. Conclusions The insufficient induction of GRP78 exerts the pro-apoptotic effect of PA-induced endoplasmic reticulum stress in hepatocellular carcinoma cells.

关 键 词：内质网应激 葡萄糖调节蛋白78 棕榈酸 凋亡 肝癌细胞 

分 类 号：R73[医药卫生—肿瘤]