CXCR4拮抗剂在肿瘤治疗中的应用  

Application of CXCR4 Antagonists in Oncotherapy

作　　者：罗竞红[1] 郭芝刚[2] 曾军[2] 

机构地区：[1]成都大学城乡建设学院,四川成都610106 [2]广州医学院基础学院,广东广州510182

出　　处：《成都大学学报（自然科学版）》2012年第4期309-315,共7页Journal of Chengdu University（Natural Science Edition）

摘　　要：G蛋白偶联趋化因子受体CXCR4在癌细胞表面广泛表达,癌细胞易转移部位的基质细胞组成型分泌CXCR4的配体——基质细胞衍生因子-1(SDF-1/CXCL12),表达CXCR4的癌细胞在CXCR4/CXCL12轴的调控下沿CXCL12浓度梯度进行转运和归巢,转移的癌细胞在CXCL12作用下与基质细胞紧密联系而获得药物抗性.CXCR4的拮抗剂,比如AMD3100,T140类似物和本课题组开发的SDF-1βP2G,能打断癌细胞与基质细胞的相互作用,动员癌细胞离开对其具保护作用的微环境从而进入血液循环系统,使癌细胞对传统药物的敏感性增加.因此,靶向CXCR4/CXCL12轴的CXCR4拮抗剂联合化疗在探索肿瘤患者治疗方面是一个新颖的,富有吸引力的方法.CXCR4, a seven-transmembrane G-protein-coupled ehemokine receptor, is expressed heavily in cancer cells. Stromal cells in which cancer cell metastasizes keep releasing a ligand for CXCR4, stromal cell-derived factor-1 （SDF-1/CXCL12）. Cancer cells expressing CXCR4 transfer and home along a gradient of the CXCL12. CXCL12 facilitates tight adhesion of cancer cells with stromal cells, which leads to drug re- sistance. CXCR4 antagonists, such as SDF-I^P2G developed by this lab, Plerixafor （AMD3100） and T140 analogs alike, can disrupt adhesive tumor-stroma interactions and mobilize cancer cells from their protective stromal microenvironment, making them more exposed to conventional anti-cancer drugs. Therefore, targeting the CXCR4-CXCL12 axis may be a novel and potential therapeutic approach in current clinical trials for tu- mor patients.

关 键 词：CXCR4 拮抗剂 肿瘤治疗 

分 类 号：R730[医药卫生—肿瘤]