项目名称： 二亚硝基哌嗪（DNP）通过CTSB调控EMT参与鼻咽癌转移的分子机制研究

项目编号： No.81502346

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 谭功军

作者单位： 暨南大学

项目金额： 18万元

中文摘要： 基于前期研究发现DNP促进鼻咽癌（NPC）转移并上调cathepsin（CTSB）和EMT标志物 Vimentin表达，分子模拟发现DNP与CTSB-papain结合。由此推断：DNP通过与CTSB结合增强CTSB表达，高CTSB调控EMT参与NPC转移。本项目拟采用分子模拟、siRNA干扰、动物实验等探讨DNP通过CTSB调控EMT参与NPC转移分子机制研究，拟开展1）检测NPC组织和转移组织CTSB及EMT标志物表达，明确其与NPC转移的关系；2）分子模拟技术分析DNP与CTSB结合，发现DNP与CTSB-papain fold结合。实验验证DNP与CTSB结合，增强CTSB表达；3）分析CTSB对细胞EMT、侵袭与转移的调控; 4) siRNA阻断CTSB，分析DNP对细胞EMT和侵袭转移调控；5)动物实验确证DNP上调CTSB介导EMT促进NPC转移。阐明鼻咽癌高转移的分子机制。

中文关键词： 鼻咽部肿瘤；组织蛋白酶B；上皮-间质细胞转化；二亚硝基哌嗪

英文摘要： Based on DNP (N,N-Dinitrosoperazine,DNP) promoting nasopharyngeal carcinoma (NPC) metastasis, upregulating expression of cathepsin B and vimentin biomarker for epithelial-mesenchymal transition（EMT）, and molecular simulation predicting the binding of DNP and CTSB-papain fold in the previous works. We can drawn from a hypothesis: DNP mediates the high expression of CTSB through binding CTSB-papain, high CTSB upregulating EMT participates in NPC metastasis. In this project, the molecular mechanisms of DNP regulation of EMT through cathepsin B involved in nasopharyngeal carcinoma metastasis are to be investgated using molecular simulation, siRNA blocking and metastasis assay in nude mice.We are to perform the follow: ①Investigating the relationship of CTSB expression, EMT and NPC metastasis in clinical; ②The interaction of DNP and CTSB is analyzed using molecular simulation, it found DNP binding to the papain domain of CTSB, and increasing CTSB expression. These findings are proved using the experiments; ③analyzing the regulation of invasion,metastasis and EMT mediated by DNP through CTSB. ④using siRNA to block cathepsin B, and then testing DNP regulation to invasion, metastasis and EMT under cathepsin B blocked;⑤ DNP regulation of EMT through cathepsin B are proved by metastasis assay in nude mice. In this present,we will clarify that DNP mediates NPC metastasis through cathepsin B regulation of epithelial-mesenchymal transition.

英文关键词： nasopharyngeal carcinoma;cathepsin B;epithelial-mesenchymal transition;N;N-Dinitrosoperazine