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小窝蛋白-1：肿瘤细胞氧化应激靶标

王文慧^1,2, 李洪艳^1,2, 屈超^1,2, 张叶军^1,2, 邹伟^1,2,*

¹辽宁师范大学生命科学学院，大连 116081；² 辽宁师范大学辽宁省生物技术与分子药物重点研发实验室，大连 116081

摘要

细胞内异常的氧化代谢是肿瘤发生的标志之一。氧化代谢过程中产生的过量活性物质可能通过诱导基因突变和激活致癌通路促进细胞癌变。因此，抗氧化治疗被认为是肿瘤防治的重要策略。小窝蛋白-1 (caveolin-1, Cav-1)是胞膜窖的重要组成蛋白质，其分子量为22~24 kDa。Cav-1不仅直接参与胞膜窖结构的形成、膜泡运输、胆固醇稳态维持，还通过其“脚手架”结构域与众多信号分子相互作用，调控细胞的生长、发育和分化，具有非常广泛的生理和病理作用。研究表明，Cav-1能够通过调节氧化应激介导多种肿瘤的发生和发展，靶向激活Cav-1还可以清除氧化应激过程中产生的活性物质。细胞氧化应激产生的活性物质反过来也可以调节Cav-1的表达、降解、翻译后修饰和其介导的膜转运。多种抗氧化剂可以调节肿瘤细胞中Cav-1介导的信号转导途径从而发挥抗肿瘤活性。本文简要综述了Cav-1及氧化应激在肿瘤发生和发展中作用的最新研究进展，旨在为临床肿瘤防治提供新思路。

关键词： 小窝蛋白-1; 氧化应激; 肿瘤

分类号：Q74

Caveolin-1: oxidative stress target in tumor cells 

WANG Wen-Hui^1,1, LI Hong-Yan^1,1, QU Chao^1,1, ZHANG Ye-Jun^1,1, ZOU Wei^1,1,*

¹College of Life Sciences, Liaoning Normal University, Dalian 116081, China

Abstract

Aberrant oxidative metabolism in cells is one of the hallmarks of cancer. Overproduction of reactive species promotes carcinogenesis by inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy is considered as an

important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, is involved in not only the formation of the caveolae, vesicular transport, maintaining cholesterol homeostasis directly, but also many cellular physiological and pathological processes including growth, regulation of mitochondrial antioxidant level, apoptosis and carcinomas by interacting with a lot of signaling molecules through caveolin scaffolding domain. Cav-1 has also been shown to mediate tumor genesis and progression through oxidative stress modulation, while Cav-1-targeted treatment could scavenge the reactive species. Intracellular reactive species could modulate the expression, degradation, post-translational modifications and membrane trafficking of Cav-1. More importantly, emerging evidence has indicated that multiple antioxidants could exert antitumor activities in cancer cells by modulating the signaling of Cav-1. This paper reviewed the research progresses on the roles of Cav-1 and oxidative stress in tumorigenesis and development, and would provide new insights on designing strategies for cancer prevention or treatment.

Key words: caveolin-1; oxidative stress; tumor

收稿日期：2019-01-16　　录用日期：2019-03-25

通讯作者：邹伟　　E-mail: weizou60@126.com

DOI: 10.13294/j.aps.2019.0047

引用本文：

王文慧, 李洪艳, 屈超, 张叶军, 邹伟. 小窝蛋白-1：肿瘤细胞氧化应激靶标[J]. 生理学报 2019; 71 (5): 792-798.

WANG Wen-Hui, LI Hong-Yan, QU Chao, ZHANG Ye-Jun, ZOU Wei. Caveolin-1: oxidative stress target in tumor cells . Acta Physiol Sin 2019; 71 (5): 792-798 (in Chinese with English abstract).