间隙连接蛋白Connexin 43介导的胶质瘤替莫唑胺耐药研究进展  

Advances of Connexin 43-mediated glioma temozolomide resistance

作　　者：覃虹锟 桂艳萍 王亚菁 赵丽[1,2] QIN Hongkun;GUI Yanping;WANG Yajing;ZHAO Li(Jiangsu Key Laboratory of Carcinogenesis and Intervention;State Key Laboratory of Natural Medicines;Department of Physiology,School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学江苏省肿瘤发生与干预重点实验室,南京210009 [2]中国药科大学天然药物活性组分与药效国家重点实验室,南京210009 [3]中国药科大学基础医学与临床药学学院生理学教研室,南京210009

出　　处：《中国药科大学学报》2018年第6期646-652,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81773774;No.81872903)~~

摘　　要：间隙连接是哺乳动物细胞间由间隙连接蛋白组成的通道,是细胞进行物质交换和信号传递的重要结构。间隙连接蛋白Connexin 43(Cx43)是中枢神经系统中表达最丰富的间隙连接蛋白。越来越多的证据表明,Cx43与胶质瘤的恶性生物学行为有着密切联系,对胶质瘤的发生发展具有广泛的调节作用。替莫唑胺是目前治疗胶质瘤的一线化疗药物,随着治疗时间延长,部分患者对其耐药并导致疾病进展,Cx43在胶质瘤中的异常表达可能是患者对替莫唑胺耐药的重要原因之一。本文就Cx43的结构与功能、替莫唑胺耐药产生的机制、Cx43介导胶质瘤替莫唑胺耐药的研究进展及以Cx43为靶点的抗肿瘤候选化合物进行综述,以期为胶质瘤治疗方案提供新的理论依据。Gap junction is a necessary channel structure composed of connexin proteins,which can form direct communication to exchange material and information between mammal cells.Connexin43(Cx43)is the most abundant connexin protein expressed in the central nervous system.There is emerging evidence that Cx43has a wide regulatory effect on the occurrence and development of glioma and play an important role in malignant biological behaviors of glioma.Temozolomide is a currently first-line chemotherapeutic drug for glioma.However,with the prolong of treatment period,the therapy effect of temozolomide is attenuated in some patients because of drug resistance.And the abnormal expression of Cx43in glioma may be one of the important reasons for temozolomide resistance.In this review,we summarized the structure and function of Cx43,several mechanism of temozolomide resistance and the research progress of Cx43-mediated temozolomide resistance,as well as anti-tumor compounds targeting Cx43in recent years,in order to provide new evidence for glioma therapy.

关 键 词：胶质瘤 间隙连接 替莫唑胺 肿瘤耐药 研究进展 

分 类 号：R965[医药卫生—药理学]