胃痞消逆转TGF-β/Smads通路介导胃癌前病变上皮-间质转化分子机制研究

项目名称： 胃痞消逆转TGF-β/Smads通路介导胃癌前病变上皮-间质转化分子机制研究

项目编号： No.81473620

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 潘华峰

作者单位： 广州中医药大学

项目金额： 76万元

中文摘要： 胃癌前病变（PLGC）有发展为胃癌的风险，阻断或逆转PLGC发展的恶性事件是降低胃癌发生率的有效措施之一。重度异型增生（HGD）胃粘膜上皮细胞（GEC）与癌干细胞具有相似性，因此HGD-GEC可用于侵袭性胃腺癌发生机制的研究。PLGC无特效治疗西药，而中药具有PLGC逆转效应，可预防胃腺癌的发生。上皮-间质转化(EMT)是异形细胞获得转移能力和耐药性等干细胞特性的关键过程。前期研究表明早期PLGC大鼠胃粘膜存在Lgr5+干细胞的早期迁移现象，可能与Wnt、IKK-3β、Notchs等介导的EMT有关，中药胃痞消具有明显逆转效应。本研究拟以TGF-β/Smadss信号通路为核心，观察PLGC大鼠和人GEC的EMT信号转导调控机制、EMT调控对Lgr5+干细胞迁移干预效应，以期阐明胃痞消干预GEC恶变为侵袭性胃腺癌的发生机制。

中文关键词： 胃痞消；胃癌前病变；上皮-间质转化；Lgr5；TGF-β/Smads通路

英文摘要： Gastric precancerous lesions (PLGC) can develop to gastric cancer,blocking or reversing the development of PLGC is one of the effective measures to reduce the incidence of stomach cancer.High grade dysplasia(HGD) is similar to cancer stem cell,so HGD could be used to study the mechanism of incidence of gastric adenocarcinoma.Traditional Chinese Medicine treat PLGC well,and it can prevent the incidence of gastric adenocarcinoma. Epithelial mesenchymal transition (EMT) is an important process that heterotypic cells obtain features of stem cells such as metastatic capacity and resistance. In previous studies, Our studies demonstrated that the phenomenon of early migration of lgr5+ stem cells might be involved in gastric epithelium from PLGC rats, which might be associated with EMT mediated by Wnt, IKK-3β, Notchs, etc. Furthermore, Weipixiao has inhibitory effects on them. In this study, based on TGF-β/Smads signaling pathway, we will explore the mechanisms of EMT-related signal transduction regulation and the effects of EMT- related Lgr5+ stem cells migration in gastric epithelium with precancerous lesions of gastric cancer, and further to reveal the mechanisms of Weipixiao on treating PLGC.

英文关键词： Weipixiao;precancerous lesions of gastric cancer;epithelial-mesenchymal transition;Lgr5;TGF-β/Smads pathway