维生素E琥珀酸酯诱导人胃癌细胞发生未折叠蛋白反应的研究

doi:10.3969/j.issn.1004-616x.2017.04.003

癌变·畸变·突变 ›› 2017, Vol. 29 ›› Issue (4): 256-259,265.doi: 10.3969/j.issn.1004-616x.2017.04.003

维生素E琥珀酸酯诱导人胃癌细胞发生未折叠蛋白反应的研究

黄晓莉¹, 吴坤², 赵莎莎¹

1. 山东大学齐鲁医院营养科, 山东济南 250012;
2. 哈尔滨医科大学营养与食品卫生教研室, 黑龙江哈尔滨 150081

收稿日期:2016-09-20 修回日期:2017-02-18 出版日期:2017-07-31 发布日期:2017-07-31
作者简介:黄晓莉,E-mail:hxl0251010@163.com
基金资助:
国家自然科学基金资助项目（81402663）

Vitamin E succinate induced unfolded protein response of human gastric cancer SGC-7901 cells

HUANG Xiaoli¹, WU Kun², ZHAO Shasha¹

1. Department of Nutrition, Qilu Hospital of Shandong University, Jinan 250012, Shandong;
2. Department of Nutrition and Food Hygiene, Harbin Medical University, Harbin 150081, Heilongjiang, China

Received:2016-09-20 Revised:2017-02-18 Online:2017-07-31 Published:2017-07-31

摘要/Abstract

摘要：

目的：探讨维生素E琥珀酸酯（VES）对人胃癌细胞未折叠蛋白反应的影响。方法：采用Western blot法分析VES不同剂量（0、5、10和20 μg/mL）处理人胃癌SGC-7901细胞24 h和20 μg/mL VES处理SGC-7901细胞不同时间（0、6、12、18和24 h）对内质网膜上的跨膜蛋白PKR样内质网蛋白激酶（PERK）磷酸化和活化转录因子6（ATF6）活化的影响；采用RT-PCR法检测VES不同剂量（0、5、10和20 μg/mL）处理SGC-7901细胞24 h和20 μg/mL VES处理SGC-7901细胞不同时间（0、3、6、9、12、15、18和24 h）对活化转录因子4（ATF4）mRNA表达和X盒结合蛋白1（XBP1）mRNA剪切的影响。结果：在翻译水平上VES对磷酸化PERK的诱导作用具有时间依赖关系，与阴性对照组比较，10 μg/mL VES的诱导作用最强（P < 0.05）；在翻译水平上VES对ATF6活化片段的诱导作用具有时间依赖关系和剂量依赖关系；在转录水平上，随着作用时间的延长，VES对ATF4 mRNA的诱导作用也不断增强，18 h达到高峰，而XBP1 mRNA从VES作用6 h即开始出现剪切。结论：VES诱导人胃癌SGC-7901细胞发生内质网应激过程中，未折叠蛋白反应相关信号分子被活化。

关键词: 未折叠蛋白反应, 维生素E琥珀酸酯, 胃癌细胞, 内质网应激

Abstract:

OBJECTIVE: To investigate the effect of vitamin E succinate (VES) on unfolded protein response (UPR) in human gastric cancer SGC-7901 cells. METHODS: SGC-7901 cells were treated with VES at 5,10 and 20 μg/mL and with tunicamycin (TM) at 3 μg/mL for 24 h or at 20 μg/mL for up to 24 h. RNA-dependent protein kinase (PKR)-like ER kinase (PERK) and activating transcription factor 6 (ATF6) were evaluated using Western blotting. X-box-binding protein 1 (XBP1) and activating transcription factor 4 (ATF4) were evaluated using RT-PCR. RESULTS: VES induced the phosphorylation of PERK in a time-dependent manner and reached the top level at 10 μg/mL. In addition, VES induced the generation of p50ATF6 in SGC-7901 cells in a dose-and time-dependent manner. Like the positive control,VES treatment at 20 μg/mL induced the spliced form of XBP1 from 6 h up to 24 h. Meanwhile,ATF4 mRNA was also up-regulated in cells exposed to VES in a time-dependent manner and reached the top level at 18 h. CONCLUSION: UPR pathways may be activated by VES in human gastric cancer SGC-7901 cells.

Key words: unfolded protein response, vitamin E succinate, gastric cancer SGC-7901 cells, endoplasmic reticulum stress

中图分类号:

R730.2

黄晓莉, 吴坤, 赵莎莎. 维生素E琥珀酸酯诱导人胃癌细胞发生未折叠蛋白反应的研究[J]. 癌变·畸变·突变, 2017, 29(4): 256-259,265.

HUANG Xiaoli, WU Kun, ZHAO Shasha. Vitamin E succinate induced unfolded protein response of human gastric cancer SGC-7901 cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(4): 256-259,265.

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维生素E琥珀酸酯诱导人胃癌细胞发生未折叠蛋白反应的研究

Vitamin E succinate induced unfolded protein response of human gastric cancer SGC-7901 cells

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