GSK-3β活性调节与肿瘤治疗  

Modulation of GSK-3β activity in cancer treatment

作　　者：陶丽[1] 盛晓波[1] 刘玉萍[1] 韦忠红[1] 王爱云[1,2] 陆茵[1,2] 

机构地区：[1]南京中医药大学药学院 [2]南京中医药大学药学院 [3]江苏省中药药效与安全性评价重点实验室,江苏南京210023

出　　处：《中国药理学通报》2014年第6期741-744,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81173174,81202655);“十一五”科技支撑计划项目(No 2008BAI51B02);教育部博士点基金(No 20113237110008);江苏省自然科学基金资助项目(No BK2010085,2010562);江苏省普通高校研究生科研创新计划项目(No CXZZ13_0627)

摘　　要：糖原合成酶激酶3β(glycogen synthase kinase 3β,GSK-3β)作为细胞内主要的丝氨酸/苏氨酸家族激酶,其活性异常与多种疾病的发生发展密切相关。值得关注的是,GSK-3β对肿瘤进程的调节是双向的,当扮演"促瘤因子"角色的GSK-3β被抑制时,不可避免阻断了其"抑瘤因子"的功能,使得Wnt/β-catenin信号通路的激活,成为目前靶向肿瘤GSK-3β引起治疗矛盾的焦点。事实上,生物学的绝缘机制可以使GSK-3β在广泛参与细胞内众多信号通路的调节中互不干扰,从而决定了细胞命运。因此,深入了解GSK-3β在不同信号系统中活性调节的具体机制,或者设计底物特异的竞争性抑制剂,对于在靶向GSK-3β的肿瘤治疗中采取选择性的权衡策略具有重大意义。As the major member of serine/threonine protein ki-nases family, glycogen synthase kinase 3β （ GSK-3β） has well characterized roles in the development of a variety of diseases. However, it is noticed that modulation of GSK-3β in tumor pro-gress is two-faced. Once the activity of GSK-3βas a“pro-onco-genic factor” is inhibited, opposing role as a“tumor suppressor”can also be disrupted, which will trigger the consequent side effect on activation of Wnt/β-catenin signaling pathway. The is-sue has placed a major obstacle to anti-GSK-3β in cancer treat-ment. In fact, functional compartmentalization of a large number of intracellular signaling events cross-talked with GSK-3β can prevent their mutual interference and determine the cell fate. Therefore, understanding the specific mechanisms of GSK-3β in regulation of diverse signaling systems or refinement of a sub-strate competitive inhibitor may have great significance to exploit approaches selectively target GSK-3β in tumor treatment.

关 键 词：糖原合成酶激酶3Β WNT Β-CATENIN信号通路 绝缘机制 药物设计 底物竞争性抑制剂 肿瘤治疗 

分 类 号：R-05[医药卫生] R329.2