3,8'-联芹菜苷元通过抑制氧连接氮乙酰葡糖胺转移酶(OGT)降低HeLa细胞迁移侵袭潜能  

3,8'-Biapigenin reduces invasiveness and migration capabilityof HeLa cells by inhibiting O-linked N-acetylglucosamine transferase(OGT)

作　　者：刘欣[1] 张娜娜[1] 曹禺 朱彤[1] 李文利[1] 张嘉宁[1] 刘宇博[1] LIU Xin;ZHANG Na-na;CAO Yu;ZHU Tong;LI Wen-li;ZHANG Jia-ning;LIU Yu-bo(School of Life Science and Pharmacy,Dalian University of Technology,Panjin Liaoning 124000,China)

机构地区：[1]大连理工大学,生命科学与药学学院,辽宁盘锦124000

出　　处：《中国药理学通报》2020年第11期1574-1580,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31971214);辽宁省自然科学基金资助项目(No 2019-MS-042,20180550426,20180550315)。

摘　　要：目的筛选具有氧连接氮乙酰葡糖胺转移酶(O-linked N-acetylglucosamine transferase,OGT)抑制活性的天然产物化合物,分析其抗肿瘤细胞迁移侵袭活性。方法对10种四氢穗花杉双黄酮天然产物类似物与OGT进行分子对接结合能分析,在无细胞反应体系中比较这些化合物的OGT抑制活性;Western blot法检测3,8'-联芹菜苷元对人宫颈癌细胞系HeLa氧连接氮乙酰葡糖胺(O-GlcNAc)修饰的抑制情况;采用细胞划痕和Transwell法观察3,8'-联芹菜苷元对HeLa细胞迁移侵袭潜能的影响。结果3,8'-联芹菜苷元具有优于四氢穗花杉双黄酮的OGT结合能和抑制活性,以时间和浓度梯度方式抑制OGT活性,降低HeLa细胞内的O-GlcNAc修饰,抑制HeLa细胞的迁移侵袭潜能。结论3,8'-联芹菜苷元能够抑制OGT活性,降低细胞内蛋白质的O-GlcNAc修饰,进而阻止肿瘤细胞迁移侵袭。Aim To screen natural product compounds with O-linked N-acetylglucosamine transferase(OGT)inhibition activity and analyze their anti-cancer cells′migration and invasion capacity.Methods The molecular docking analysis of 10 Tetrahydroamentoflavone analogues was performed.The OGT inhibitory activities of these compounds were compared in a cell-free reaction system.Western blot was used to assess theinhibitionof HeLa O-linked acetylacetylglucosamine(O-GlcNAc)modificationin human cervical cancer cell line HeLa.The cell wound scratch and Transwell assay were used to observe the infection of 3,8'-Biapigenin on the migration and invasion potential of HeLa cells.Results 3,8'-Biapigenin had better OGT binding energy and inhibitory activities than Tetrahydroamentoflavone did.3,8'-Biapigenin inhibited OGT activity in a time and dose-dependent manner.This compound reduced O-GlcNAc modification in HeLa cells and inhibited HeLa cell migration and invasion.Conclusions 3,8'-Biapigenin can inhibit OGT activity and reduce O-GlcNAc modification of cancer cells,which accordingly prevents cancer cells from migrating and invading.

关 键 词：氧连接氮乙酰葡糖胺转移酶抑制剂 迁移侵袭 天然产物 糖基化 活性检测 抑制率 

分 类 号：R285.5[医药卫生—中药学] R329.24[医药卫生—中医学]