RORα拮抗剂T0901317通过RORα/β-catenin信号促进人胃癌MGC803细胞上皮间质转化  

RORα antagonist T0901317 promotes EMT in human gastric cancerMGC803 cells by RORα/β-catenin signal

作　　者：张翼臻 裴大兵 苏坚[1,3] 刘芳 夏红[1] 苏琦[1] ZHANG Yi-zhen;PEI Da-bing;SU Jian;LIU Fang;XIA Hong;SU Qi(Hunan Key Laboratory of Cancer Cellular and Molecular Pathology,Cancer Research Institute,University of South China,Hengyang Hunan 421001,China;the Affiliated Hospital,Jinggangshan University,Ji′an Jiangxi 343000,China;Hunan Clinical Research Center for Gastric Cancer Prevention and Treatment,Dept of Pathology,the Affiliated Second Hospital,University of South China,Hengyang Hunan 421001,China)

机构地区：[1]南华大学肿瘤研究所,湖南省肿瘤细胞与分子病理学重点实验室,湖南衡阳421001 [2]井冈山大学附属医院病理科,江西吉安343000 [3]湖南省胃癌防治临床研究中心,南华大学附属第二医院病理科,湖南衡阳421001

出　　处：《中国药理学通报》2023年第4期631-637,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81374013,81641112);吉安市科计字2021-8号-98;江西省中医药管理局科技计划项目(No 2021B715)。

摘　　要：目的 探讨RORα拮抗剂T0901317通过RORα/β-catenin信号对促进人胃癌MGC803细胞上皮-间质转化(epithelial–mesenchymal transition, EMT)的影响。方法 MTT检测细胞增殖;细胞划痕和Transwell实验分别检测细胞迁移与侵袭。Western blot与免疫荧光检测RORα/β-catenin信号相关分子,免疫共沉淀检测RORα蛋白与β-catenin蛋白结合。结果 MTT检测显示,T0901317处理组较MGC803细胞增殖能力呈时间依赖性增加(P<0.05)。细胞划痕和Transwell实验显示,T0901317处理组细胞迁移与侵袭能力较MGC803细胞明显增强(P<0.05)。Western blot检测显示,T0901317处理后较未处理组RORα蛋白明显下调(P<0.05),并且可上调MGC803细胞β-catenin总蛋白与核内β-catenin(P<0.05)。T0901317处理后较对照组RORα蛋白与β-catenin蛋白结合分别明显减少(P<0.05)。T0901317处理的细胞较未处理MGC803细胞的长梭形细胞增加,异型性更为明显。T0901317可明显上调MGC803细胞Rac1、TGF-β1、Vimentin的表达(P<0.05),并抑制E-cadherin的表达(P<0.05)。结论 T0901317可通过RORα/β-catenin信号促进人胃癌MGC803细胞增殖、迁移侵袭与EMT。Aim To investigate the effect of RORαantagonist T0901317 promoting EMT(epithelial–mesenchymal transition)of human gastric cancer MGC803 cells by RORα/β-catenin signal.Methods Cell proliferation was detected by MTT.Cell migration and invasion were detected by cell scratch and Transwell assay respectively.RORα/β-catenin signaling molecules were detected by Western blot and immunofluorescence.RORαbinding toβ-catenin protein was detected by immunoprecipitation.Results MTT assay showed that the proliferation ability of T0901317 cells increased in a time-dependent manner compared with MGC803 cells(P<0.05).Cell scratches and Transwell experiments showed that the migration and invasion ability of T0901317 cells were significantly enhanced compared with MGC803 cells(P<0.05).Western blot analysis showed that RORαprotein was significantly down-regulated after T0901317 compared with untreated group(P<0.05),and totalβ-catenin protein and nuclearβ-catenin in MGC803 cells were up-regulated after T0901317(P<0.05).Compared with the control group,RORαprotein binding toβ-catenin protein significantly decreased after T0901317 treatment(P<0.05).Compared with MGC803 cells treated with T0901317,the long spindle cells increased and the heteromorphism was more obvious.T0901317 significantly up-regulated the expression of Rac1,TGF-β1 and Vimentin in MGC803 cells(P<0.05),and inhibited the expression of E-cadherin(P<0.05).Conclusion T0901317 can promote the proliferation,migration,invasion and EMT in human gastric cancer MGC803 cells by RORα/β-catenin signal.

关 键 词：RORα T0901317 人胃癌MGC803细胞 RORα/β-catenin信号 增殖 上皮-间质转化 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学] R735.2[医药卫生—基础医学] R735.202.2R916.4