Smac与肿瘤放射治疗

放射治疗是肿瘤治疗的一个重要手段，肿瘤的辐射敏感性与凋亡蛋白抑制家族(IAPs)和促凋亡蛋白第二线粒体来源的Caspase激活因子(Smac)密切相关。IAPs能够通过结合Caspase-3、7、9抑制凋亡，IAPs的高表达是肿瘤细胞出现辐射抵抗的重要机制之一。当细胞接收到凋亡刺激信号后，Smac即从线粒体释放至胞质内与IAPs结合从而释放Caspase，发挥其促凋亡活性。以IAPs为靶点的治疗可能会为肿瘤细胞克服放射抵抗打开新的视角。临床前的体内体外研究证明，这种联合治疗值得更进一步的临床研究。使用IAPs拮抗剂联合放射治疗可能会为更有效的放射治疗肿瘤患者铺平道路。

Effects of Smac on tumor radiotherapy

Radiotherapy is one of the main methods of tumor therapy. The radiosensitivity of tumor is closely related to inhibitor of apoptosis proteins(IAPs)and the second mitochondria-derived activator of Caspase(Smac). IAPs can inhibit apoptosis by binding and inhibiting Caspase-3, 7, 9. High expression of IAPs has been shown to interfere with the efficacy of radiotherapy. Smac, upon apoptotic stimuli, is released into the cytoplasm to inhibit the caspase-binding activity of IAPs. Therapies targeting of IAP proteins may show new perspectives to overcome radioresistance. In vitro and in vivo preclinical studies have demonstrated that the combination approach warranted further clinical investigation. Thus, combination protocols using IAPs antagonists together with radiotherapy may pave the avenue to more effective radiation-based treatment options for tumor patients.