Par－4特异诱导肿瘤凋亡及其机制的研究新进展

摘要

Prostate apoptosis response gene-4(par-4)was first identified from the prostate tissue.This gene can express in both normal and cancer cells.The translation product of par-4 is prostate apoptosis response protein-4 ( Par-4 ) , which is unique in its ability to selectively induce apoptosis in cancer cells while leaving the normal cells unaffected through intracellular and extracellular pathway.Par-4 is cleaved and phosphorylated by caspase3 and PKA; Par-4 transportsFas/FasL tocell membrane and activation of pro-apoptotic pathway;intracellular Par-4 transports GPR78 to cell membrane;extracellular Par-4 binds to GRP78 and activates it.There is a significant potential role in anti-tumors therapy of extracellular Par-4.The latest research progress on the mechanism of apoptosis induced by Par-4 and the treatment of exogenous Par-4 in tumor was discussed in this article.%前列腺凋亡反应基因－4（prostate apoptosis response gene－4，par－4）基因是最早在前列腺癌细胞中发现，这个基因在正常细胞和肿瘤细胞中均可表达，其编码产物前列腺凋亡蛋白－（ prostate apoptosis response protein，Par－4）可通过内源性和外源性途径选择性的诱导肿瘤细胞凋亡，而对正常细胞没有影响。 Par－4发挥作用可包括内源性Par－4裂解和磷酸化、内源性Par－4转运Fas／FasL并激活Fas／FasL促凋亡通路、及外源性的Par－4和细胞膜上的GPR78结合诱导细胞凋亡等过程。特别是Par－4的外源性途径在肿瘤的靶向治疗中有很重要的应用价值。本文就Par－4诱导凋亡机制及外源性Par－4在肿瘤治疗方面的最新研究进展进行综述。