蛋白酶体抑制剂MG132对卵巢癌作用机制的研究现状  

Research status on mechanism of proteasome inhibitor MG132 on ovarian cancer

作　　者：岳驰 刘辉 刘星辰 魏宝宝 郭娜 Yue Chi;Liu Hui;Liu Xingchen;Wei Baobao;Guo Na(Department of Obstetrics and Gynecology,Chengdu Women′s and Children′s Central Hospital,Chengdu 610031,Sichuan Province,China;Department of Obstetrics and Gynecology,Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University),Ministry of Education,West China Second University Hospital,Sichuan University,Chengdu 610041,Sichuan Province,China)

机构地区：[1]成都市妇女儿童中心医院妇产科,610031 [2]四川大学华西第二医院妇产科、出生缺陷与相关妇儿疾病教育部重点实验室,成都610041

出　　处：《中华妇幼临床医学杂志（电子版）》2018年第6期629-635,共7页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：四川省卫生计生委科研课题(普及应用项目)(16PJ236)~~

摘　　要：泛素蛋白酶体途径(UPP)和自噬溶酶体途径(ALP)是真核细胞内蛋白质降解的2种重要途径。MG132是一种可逆性肽醛类蛋白酶体(proteasome)抑制剂,可进入细胞中可逆性抑制蛋白酶体活性,抑制UPP介导的蛋白质降解,从而诱导细胞凋亡。自噬性细胞死亡是一种不同于细胞凋亡的程序性死亡,细胞自噬是细胞利用溶酶体降解自身受损的大分子物质和细胞器的生理性细胞死亡过程。卵巢癌是女性生殖系统三大恶性肿瘤之一。晚期卵巢癌患者的5年生存率约为47%,是妇科恶性肿瘤中导致患者死亡率最高的肿瘤。MG132可通过调节凋亡蛋白表达,促进卵巢癌细胞凋亡,但是否可通过调控凋亡、自噬蛋白表达,促进卵巢癌细胞死亡,则迄今文献报道较少。笔者拟就蛋白酶体抑制剂MG132对卵巢癌的作用机制的最新研究现状进行阐述,旨在为MG132治疗卵巢癌提供理论基础。The ubiquitin-proteasome pathway(UPP)and autophagy-lysosome pathway(ALP)are two major ways of protein degradation in eukaryotic cells.MG132(Z-Leu-Leu-CHO)is a reversible peptide aldehyde proteasome inhibitor,which can enter into cells and reversibly inhibiting proteasome activities,thus inhibiting protein degradation mediated by UPP,affecting the course of cell cycle and inducing apoptosis of cells.Autophagic cell death is a type of programmed cell death different from apoptosis.Autophagy is a process of physiological cell death by using the lysosomes to degrade their own damaged macromolecules and organelles.Ovarian cancer is one of the three malignant tumors of female reproductive system.The 5-year survival rate of advanced ovarian cancer is about 47%,which is the highest mortality rate in gynecologic malignancies.It has been reported that MG132 can promote apoptosis of ovarian cancer cells by regulating the expression of apoptotic protein,but it is rare to report whether it can promote cell death of ovarian cancer cells by regulating the expression of apoptotic and autophagic protein.This review demonstrates the latest research status of mechanism of MG132 on ovarian cancer in order to provide a theoretical basis for the treatment of ovarian cancer by MG132.

关 键 词：卵巢肿瘤 蛋白酶抑制药 MG132 细胞凋亡 自噬 泛素蛋白酶体途径 自噬溶酶体途径 女(雌)性 

分 类 号：R737.31[医药卫生—肿瘤]