SREBP-1及其抑制剂调节肿瘤代谢的研究进展  

The recent development of SREBP-1 and SREBP-1 inhibitors in regulation of cancer metabolism

作　　者：张葳蕤[1,2] 刘小宇[1,2] 于豪冰[1,2] 卢小玲[1,2] 焦炳华[1,2] ZHANG Wei-rui;LIU Xiao-yu;YU Hao-bing;LU Xiao-ling;JIAO Bing-hua(Marine Biopharmaceutical Institute, Second Military Medical University, Shanghai 200433, China;Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China)

机构地区：[1]第二军医大学海洋生物医药研究中心,上海200433 [2]第二军医大学基础部生物化学与分子生物学教研室,上海200433

出　　处：《肿瘤代谢与营养电子杂志》2017年第1期114-119,共6页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家自然科学基金(41306197;41606173)

摘　　要：脂类作为三大营养物质之一,参与能量的供应和储存、细胞的构建和作为活性分子参与细胞生命活动。脂类代谢异常是肿瘤细胞的重要特征之一,主要表现为脂肪酸从头合成及氧化代谢活跃,这些改变与肿瘤信号通路增强,相关代谢酶改变等密切相关。目前,脂代谢通路中相关酶及转录因子成为肿瘤治疗的潜在药物靶点。SREBP-1是细胞内调控脂类代谢的关键转录因子,主要调控胆固醇和脂肪酸合成中关键酶基因的表达,调节脂质新生。SREBP-1及其调控的脂肪酸合成途径通常在正常组织和细胞中的表达和活性较低,在肿瘤细胞中,SREBP-1被激活,其下游基因的表达也升高,在加快胞内脂肪酸和胆固醇合成的同时,还通过细胞内各信号通路影响肿瘤细胞脂代谢、糖代谢以及氨基酸代谢,为维持肿瘤细胞的增殖和转移提供额外的能源和物质。运用遗传和药理手段抑制肿瘤细胞中SREBP-1的表达和活化,可显著抑制体内和体外多种肿瘤细胞的增殖和迁移。因此,SREBP-1将是一个有潜力的针对肿瘤细胞脂代谢的肿瘤治疗靶标。本文综述了SREBP-1在肿瘤中的异常表达对肿瘤信号通路和物质代谢的影响以及SREBP-1抑制剂在肿瘤中的研究进展。Lipids,one of the three major nutrients,plays an important role in supplying and storing energy,constructing cells and taking part in cell life activities as an active molecule.One of the most important characteristics of cancer metabolism is the abnormal lipid metabolism,showing the denovo fatty acid synthesis and the active oxidative metabolism,which are closely related to the enhancement of tumor signal transduction pathway and the change of metabolic enzymes.Recently,the related enzymes and transcription factors in the lipid metabolism pathway are potential drug targets for cancer therapy.SREBP-1is a key transcription factor which regulates the expression of key enzymes in cholesterol or fatty acids synthesis and controls lipogenesis.The expression and activity of SREBP-1and its regulated fatty acid synthesis pathway are low in normal tissues and cells,while SREBP-1is activated,accompanying the increase of the downstream gene expression in the tumor cells,which accelerate the synthesis of intracellular fatty acids and cholesterol and regulate lipid metabolism,glucose metabolism and amino acid metabolism viaintracellular signaling pathways to provide additional energy and substrates to maintain proliferation and metastasis of tumor cells.The expression and activation of SREBP-1in tumor cell can be inhibited by genetic and pharmacological means,which significantly suppress the proliferation and migration of tumor cells in vivo and in vitro.Therefore,SREBP-1has emerged as a promising tumor therapeutic target.In this paper,the effects of abnormal expression of SREBP-1on tumor signal pathway and metabolism and the development of SREBP-1inhibitors as anti-cancer agents in cancer were reviewed.

关 键 词：SREBP-1 SREBP-1抑制剂 脂代谢 信号通路 肿瘤 

分 类 号：R730.2[医药卫生—肿瘤]