X连锁凋亡抑制蛋白的功能及其在肿瘤中的作用

The Effect of XIAP and Its Application in Tumor

X连锁凋亡抑制蛋白(X-linked inhibitor of apoptosis,XIAP)是目前发现的最具特征性与作用最强的内源性凋亡抑制蛋白质。XIAP特征性结构是其BIR结构域和RING结构域,它们都是XIAP发挥抗凋亡作用的重要结构。多种内源性抑制蛋白质(XAF1、Smac和Omi)能通过不同的方式抑制XIAP的抗凋亡作用。XIAP能直接抑制胱天蛋白酶凋亡途径的起始至持续阶段,通过直接结合胱天蛋白酶、激活NF-κB途径及其它信号途径等多种方式,参与抑制细胞凋亡的死亡受体途径和线粒体途径,对调控肿瘤细胞的生存和发展必不可少。XIAP在多种肿瘤组织中高表达。XIAP的高表达还与肿瘤的发生发展、耐药性、治疗及愈后密切相关。XIAP缺失会明显降低肿瘤细胞的成瘤性。同时,XIAP阻断多个信号通路汇集而成的细胞凋亡下游。因此,XIAP已成为临床上抗癌药物设计的一个新靶点。目前,临床上采用XIAP治疗肿瘤的3个方向为小分子抑制剂、反义寡核苷酸类抑制剂以及XIAP基因沉默。本文将从XIAP抗细胞凋亡的生物学功能及其在肿瘤疾病的发生发展、耐药性、治疗及预后中的作用作一介绍。

It has been found that X-linked inhibitor of apoptosis(XIAP)is the most characteristic and strongest inhibition of apoptosis proteins.The characteristic structures of XIAP are BIR domain and RING domain,which are important structures for XIAP to play an anti-apoptotic role.A variety of endogenous inhibitory proteins(XAF1,SMAC and OMI)can also inhibit XIAP’s anti-apoptotic effect in different ways.XIAP can directly inhibit the initiation and persistence of apoptosis pathway of caspase.XIAP participates in the death receptor pathway and mitochondrial pathway of inhibiting apoptosis in a variety of ways,such as directly binds to caspases,and activates NF-кB way and other signal pathways,which is essential for regulating the survival and development of tumor cells.XIAP is highly expressed in many kinds of tumor tissues.The high expression of XIAP is closely related to the occurrence and development,drug resistance,treatment and prognosis of tumors.XIAP deletion can significantly reduce the tumorigenicity of tumor cells,and XIAP is the downstream factor of cell apoptosis formed by blocking multiple signal pathways.Therefore,XIAP has become a new target for clinical anticancer drug design.At present,three potential directions of XIAP application in clinical treatment of cancer are small molecule inhibitors,antisense oligonucleotide inhibitors and XIAP gene silencing.This paper will introduce the biological function of XIAP against apoptosis and its role in the occurrence and development,drug resistance,treatment and prognosis of tumor diseases.