三维数控肿瘤细胞EMT微流控芯片的构建及其初步应用

项目名称： 三维数控肿瘤细胞EMT微流控芯片的构建及其初步应用

项目编号： No.81201825

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 潘小艳

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 癌症是威胁人类生命的"二号杀手"，其中肿瘤细胞侵袭转移是病情恶化的重要标志，而上皮间质转化（EMT）是其转移的前兆。传统研究肿瘤细胞EMT的方法存在一定的局限性，而微流控芯片技术具有数控、微量、三维、实时培养细胞等优点，能弥补其不足。本项目拟构建并优化可用于研究肿瘤细胞EMT并集成数控在线转染模块的微流控芯片；以胃癌细胞株为模型，利用三维共培养的间质细胞和血管内皮细胞诱导胃癌细胞发生EMT；通过数控在线转染针对Smad4的RNA干扰片段，对胃癌细胞EMT经典通路实施阻抑；并用TGF-β单克隆抗体和靶向药舒尼替尼进行干预，反向抑制胃癌细胞发生EMT；最后，综合考察该芯片的性能，为下一步肿瘤细胞EMT机制研究提供可靠的技术支撑。该芯片的成功研制，将为临床弥足珍贵的新鲜肿瘤组织细胞进行EMT研究提供有效手段。

中文关键词： 肿瘤；上皮间质转化；微流控芯片；三维；数控

英文摘要： Cancer is considered as "the second killer" that has threatened human lives. One significant sign of cancer malignancy is cell invasion and metastasis, and the precursor of metastasis,however,is highly associated with Epithelial-Mesenchymal Transition (EMT).Right now the means of EMT research in carcinoma remains limited, microfluidic chip then can compensate for this limitation with its merits of CNC, trace, three-dimention and real-time cell culture,etc.Our program is aimed to construct and optimize the microfluidic chip which integrating with numerical control on-line transfection module for EMT studying in tumors; With gastric cancer cells as cell models,we will use the co-cultured mesenchymal cells and vascular endothelial cells in three-dimemtional (3D) to induce EMT of these model cells; The EMT canonical pathway in gastric cancer cells will be blocked via numerical control on-line transfection of Smad4 RNA interfering fragments; Furthermore,monoclonal antibody against TGF-β and targeting drug,Sunitinib,will be performed to intervene and therefore inhibit the process of EMT in gastric cancer cells in reverse; Eventually, a comprehensive evaluation of this chip's performance would be provided, and it would provided solid technical support for next-step investigation of the EMT mechnisms in tumors. In co

英文关键词： Tumor；EMT；Microfluidic chip；3D；Numerical Control