《生命科学》 2016, 28(11): 1347-1352

Smac与肿瘤的放化疗增敏

姚　明，王　彦，徐　畅，刘　强*

(中国医学科学院放射医学研究所，天津市放射医学与分子核医学重点实验室，天津 300192)

摘　要：摘　要：Smac (second mitochondria-derived activator of Caspase) 是一种内源性促进细胞凋亡的蛋白，主要通过拮抗凋亡抑制因子(inhibitor of apoptosis proteins， IAPs) 对Caspase 的抑制，以及促进Caspase 的催化活性从而促进凋亡，并可通过与IAPs 的作用参与NF-кB 的调控。IAPs 在肿瘤的发生、迁移以及耐药、辐射抗性的形成中发挥重要的作用。肿瘤细胞中IAPs 的高表达与其抵抗凋亡的作用相关。因此，探究Smac 对IAPs 的拮抗作用和对Caspase 的激活机制，能够进一步阐明肿瘤细胞抗凋亡机制和其他死亡途径的逃逸机制。阐述了Smac 蛋白的结构、与IAPs 的相互作用以及Smac 模拟物作为肿瘤放化疗增敏剂的研究。

Smac and cancer chemoradiotherapy

YAO Ming， WANG Yan， XU Chang， LIU Qiang*

(Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine， Institute of Radiation Medicine， Chinese Academy of Medical Sciences and Peking Union Medical College， Tianjin 300192， China)

Abstract: Abstract: Smac (second mitochondria-derived activator of Caspase) is an endogenous protein that interacts with IAPs to antagonize its inhibition of Caspase， then promoting apoptosis and regulating NF-кB. IAPs has been reported to associate with tumorgenesis， cancer invasion and cancer drug/radiation resistance. The high level expression of IAPs is associated with the silencing of Caspase-induced apoptosis in tumor cells. Thus research on the interaction between Smac and IAPs as well as the mechanism of Caspase activation by Smac is one of new therapeutic strategies for cancer therapy. This review focuses on the structure and biological characteristics of Smac， and its interaction with IAPs， and Smac mimetics as a chemo/radiosensitization agent.