小分子药物ACT001抑制人脑胶质母细胞瘤U118MG细胞系迁移作用机制的研究  

Study on the Mechanism of Small Molecule Drug ACT001 Inhibiting Migration of Glioblastoma U118MG

作　　者：孙宇 李秋影 龚建苗 陈悦[2] 吴震州[1] 赵立青[1] Sun Yu;Li Qiuying;Gong Jianmiao;Chen Yue;Wu Zhenzhou;Zhao Liqing(College of Life Sciences,Nankai University,Tianjin 300071,China;College of Pharmacy,Nankai University,Tianjin 300353,China;Accendatech Company Limited,Tianjin 300384,China)

机构地区：[1]南开大学生命科学学院,天津300071 [2]南开大学药学院,天津300353 [3]尚德药缘有限公司,天津300384

出　　处：《南开大学学报（自然科学版）》2022年第2期1-6,共6页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：国家自然科学基金(82073119,81772687)。

摘　　要：脑胶质母细胞瘤(Glioblastoma,GBM)是脑肿瘤中最具致命性的高等级脑胶质瘤,目前尚无有效治愈药物.ACT001属于倍半萜内酯化合物,目前已进入Ⅰ期临床试验阶段,对脑胶质母细胞瘤有着很好的疗效,然而作用机制并不明确.本研究探究了ACT001作用脑胶质母细胞瘤的机制,发现ACT001可显著降低人脑胶质母细胞瘤U118MG的迁移能力,并下调STAT3通路相关蛋白的表达,且沉默STAT3蛋白后,U118MG迁移能力以及相关迁移蛋白的表达水平也同样受到影响.结果表明,ACT001可通过下调STAT3蛋白进而影响其下游Twist1和ZEB1迁移相关蛋白的表达水平,最终对U118MG细胞的迁移产生抑制作用.Glioblastoma(GBM) is the most deadly high-grade glioma in brain tumors, and there is currently no effective cure. Therefore, it is necessary to develop new drugs to treat this tumor. ACT001 is a sesquiterpene lactone compound and has entered Phase I clinical trials. It has a good effect on glioblastoma, while the mechanism of this medicine is not clear. This study explored the mechanism of ACT001 on glioblastoma. ACT001 can significantly reduce the migration of U118MG and down-regulate STAT3 pathway related proteins. Moreover, knockdown of STAT3 could also affect U118MG migration capacity and the level of migratory protein regulated by STAT3 is also affected. The results showed that ACT001 inhibited the migration of U118MG cells by down-regulating STAT3 protein and affecting the levels of Twist1 and ZEB1,which are STAT3 downstream migration-related proteins.

关 键 词：ACT001 脑胶质母细胞瘤 细胞迁移 STAT3 

分 类 号：R914[医药卫生—药物化学]