文章摘要

DADS 胃癌细胞中NADPH 氧化酶的作用及其调控机制

作者: 1,2刘锋, 2谢黎明, 2张志伟, 1邬力祥
1 中南大学公共卫生学院，湖南 长沙 410078
2 南华大学肿瘤研究所，湖南 衡阳 421001
通讯: 邬力祥 Email: ywlx@csu.edu.cn
DOI: 10.3978/.10.3978/j.issn.1005-6947.2015.10.010
基金: 国家自然科学基金资助项目, 31100935

摘要

目的：探讨二烯丙基二硫（DADS）对胃癌细胞NADPH 氧化酶活性的影响及其机制。方法：用DADS 作用于胃癌AGS 细胞后，检测细胞NADPH 氧化酶活性与miR-34a 的表达，以及Src-Gab1-Shp2 通路的活性，期间采用不同的干预，分析NADPH 氧化酶、miR-34a、Src-Gab1-Shp2 通路之间的关系。结果：DADS 作用后，AGS 细胞NADPH 氧化酶活性以及miR-34a 表达均明显升高（均P<0.05），而DADS 升高NADPH 氧化酶活性的作用被添加Src 激酶抑制剂PP2 所取消；DADS 或miR-34a 作用后，AGS 细胞Src、Gab1、Shp2 mRNA 的表达均明显降低（均P<0.05），且DADS 作用后，AGS 细胞中磷酸化Src、Gab1、Shp2 蛋白水平明显降低（均P<0.05）。结论：DADS 能升高NADPH 氧化酶活性，该作用可能与其上调miR-34a 表达，从而抑制Src-Gab1-Shp2 通路活性有关。
关键词： 胃肿瘤 氨基酸类，硫 微RNAs

Effect of Diallyl disulfide on NADPH oxidase activity in gastric cancer cells and its regulatory mechanism

Authors: 1,2LIU Feng, 2XIE Liming, 2ZHANG Zhiwei, 1WU Lixiang
1 School of Public Health, Central South University, Changsha 410078, China
2 Institute of Cancer research, University of South China, Hengyang, Hunan 421001, China

CorrespondingAuthor:WU Lixiang Email: ywlx@csu.edu.cn

Abstract

Objective: To investigate the effect of diallyl disulfide (DADS) on NADPH oxidase activity in gastric cancer cells and the mechanism. Methods: In gastric cancer AGS cells after exposure to DADS, the NADPH oxidase activity and miR-34a expression as well as the status of Src-Gab1-Shp2 pathway in the cells were detected. Meanwhile, several interventions were made to investigate the relationship among NADPH oxidase, miR-34a, and Src-Gab1-Shp2 pathway. Results: The NADPH oxidase activity and miR-34a in AGS cells were significantly increased after DADS treatment (both P<0.05), and the NADPH oxidase activity increasing effect of DADS was abolished by Src inhibitor PP2 addition. The mRNA expressions of Src, Gab1 and Shp2 were all significantly decreased after DADS or miR-34a mimics treatment, moreover, the expression levels of phosphorylated Src, Gab1 and Shp2 proteins were all significantly down-regulated after DADS treatment (all P<0.05). Conclusion: DADS can increase NADPH oxidase activity in gastric cancer cells, and this effect may probably be associated with its increasing miR-34a expression and thereby, inhibiting the activity of Src-Gab1-Shp2 pathway.
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