三氧化二砷对肝细胞癌HepG2细胞系作用效果的代谢组学研究  

Metabolomics study of the effect of arsenic trioxide on hepatocellular carcinoma cell line HepG2

作　　者：黄巾帼 张海南 陈子卿 杨丽娜 郭书娟 陶生策 HUANG Jin-guo;ZHANG Hai-nan;CHEN Zi-qing1;YANG Li-na;GUO Shu-juan;TAO Sheng-ce(Shanghai Center for Systems Biomedicine,Key Laboratory of Systems Biomedicine(Ministry of Education),Shanghai Jiao Tong University,Shanghai 200240,China;of Integrative Oncology,Fudan University Shanghai Cancer Center,Shanghai 200032,China)

机构地区：[1]上海交通大学系统生物医学研究院,系统生物医学教育部重点实验室,上海200240 [2]复旦大学附属肿瘤医院中西医结合科,上海200032

出　　处：《上海交通大学学报（医学版）》2018年第10期1145-1151,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家重点研发计划(2016YFA0500600);国家自然科学基金(31670831)。

摘　　要：目的·从代谢组学的角度揭示三氧化二砷(arsenic trioxide,ATO)对肝细胞癌(hepatocellular carcinoma,HCC)的作用机制。方法·分别取ATO处理12、24和36 h的肝细胞癌HepG2细胞系,通过气相色谱/质谱联用和液相色谱/串联质谱联用对其代谢物谱进行全局性分析。结果·共检测到307种代谢物。生物信息学分析表明,糖基化和单碳代谢是主要受影响的细胞功能。其他细胞功能或途径如线粒体脂肪酸β-氧化、三羧酸循环、戊糖磷酸途径和谷胱甘肽代谢等也受到影响。结论·ATO通过影响HepG2细胞主要的代谢途径,抑制细胞生长和迁移,并加剧氧化应激来诱导癌细胞凋亡。Objective·To reveal the mechanism of the effect of arsenic trioxide(ATO)on hepatocellular carcinoma(HCC)cells through metabolomics study.Methods·HCC cell line HepG2 was treated with ATO for 12 h,24 h and 36 h respectively.The global metabolite profiles were monitored by metabolomics analysis using GC/MS and LC/MS/MS.Results·A total of 307 certified metabolites were detected.Bioinformatics analysis showed that glycosylation and one-carbon metabolism were the main cellular functions that have been affected.Other affected cellular functions/pathways included mitochondrial function fatty acidβ-oxidation,TCA cycle,pentose phosphate pathway(PPP)and glutathione metabolism.Conclusion·ATO treatment affects the main metabolomic pathway of HepG2,and inhibits cell growth and migration,then exacerbates oxidative stress to induce cancer cell apoptosis.

关 键 词：砷剂 三氧化二砷 肝细胞癌 HEPG2 代谢组学 

分 类 号：R735.7[医药卫生—肿瘤]