Bcl-2与IP3R相互作用调控肿瘤细胞程序性死亡的研究进展  

IP3R/Bcl-2-channel complexes regulates programmed cell death

作　　者：顾文文[1] 施韬[1] 顾一骅[1] 杨军[1] 

机构地区：[1]上海生殖健康药具工程技术研究中心,上海市计划生育科学研究所药物室,上海200032

出　　处：《肿瘤》2013年第8期743-747,共5页Tumor

摘　　要：由1,4,5三磷酸肌醇受体(inositol1,4,5-trisphosphate receptor,IP3R)介导的细胞内钙离子释放在细胞生理学过程中具有中枢性作用,其通道活性受到复杂信号网络的精细调节。近来有研究发现,IP3R是抗凋亡分子B细胞性淋巴瘤-2(B cell lymphoma-2,Bcl-2)家族蛋白的一个作用靶点,而抗凋亡Bcl-2蛋白作为IP3R的内源性调节分子,具有控制内质网中IP3R活性和抑制促凋亡钙信号的功能。已有研究证实,基于干扰Bcl-2家族成员与IP3R相互作用功能区域的多肽分子具有一定的抗肿瘤作用,因此,根据Bcl-2蛋白分子的结构特征及其与IP3R的相互作用机制而设计的靶向药物,已成为抗肿瘤新药的一个重要发展方向,并且部分药物已进入临床研究阶段。这些处于研发中的新药有望为慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)等Bcl-2依赖性肿瘤的治疗及对抗Bcl-2介导的化疗放疗耐药现象带来新希望。本文旨在对上述研究的进展作一综述,以期为肿瘤细胞程序性死亡的调控机制的研究提供一些有价值的参考依据。The Ca2＋ release through IP3R （inositol 1,4,5-trisphosphate receptor） channels mediates the essential procedure of cellular functions.The process of Ca2＋ release is elaborately regulated by the complex network system of signal transduction pathway.Recently,anti-apoptotic Bcl-2 proteins were reported to modulate Ca2＋ gating of IP3R in ER （endoplasmic reticular） resulting in enhanced cellular bioenergetics and death resistance.Targeting Bcl-2-IP3R interaction was found to be able to induce apoptosis in vitro and in vivo .In addition,the natural or chemically synthesized compounds depending on the molecular structure of anti-apoptotic Bcl-2 proteins,have been tested in several clinical trials of chronic lymphocytic leukemia to verify their anti-tumor effect.Overall,current studies have provided some novel strategies of anti-tumor therapy involved in the functional enhancement of anti-apoptotic Bcl-2 proteins or intracellular Ca2＋ signaling.

关 键 词：肿瘤 细胞凋亡易感蛋白质 磷脂酰肌醇磷酸盐类 钙信号 

分 类 号：R73-36[医药卫生—肿瘤]