分子显像监测TIGAR调节微环境诱导肿瘤转移及分子机制

项目名称： 分子显像监测TIGAR调节微环境诱导肿瘤转移及分子机制

项目编号： No.81471687

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： 刘建军

作者单位： 上海交通大学

项目金额： 70万元

中文摘要： 靶向代谢重组已经成为抗肿瘤治疗的一个重要策略。本课题通过18F-FDG micro PET/CT观察荷瘤小鼠不同TIGAR表达状态下，肿瘤组织生长与转移能力的变化，研究TIGAR蛋白表达与肿瘤细胞转移生物学行为之间相关性。通过99Tcm-3PRGD2显像观察荷瘤小鼠不同TIGAR表达状态下，肿瘤组织新生血管表达变化，研究TIGAR蛋白表达与肿瘤新生血管生成之间相关性及分子机制。通过同位素标记葡萄糖流量分析和海马生物能量测定仪观察不同TIGAR表达状态下肿瘤细胞碳流量变化、细胞酸环境变化，研究TIGAR蛋白表达与细胞酸环境变化之间相关性及分子机制。建立通过靶向肿瘤细胞调节糖酵解水平抑制肿瘤细胞血管生成诱导转移的理论体系，为临床联合应用抗代谢药物和抗血管生成药物治疗肿瘤奠定理论基础。

中文关键词： 分子显像；葡萄糖代谢；肿瘤转移

英文摘要： Targeting metabolic reprogramming has become an important strategy for tumor treatment. Tumor growth and metastasis of tumor bearing mice with different TIGAR expression condition was observed by the 18F-FDG micro PET/CT.The correlation between tumor metastasis and expression of TIGAR protein was analysed. Angiogenesis of tumor bearing mice with different TIGAR expression condition was observed by 99Tcm-3PRGD2 imaging. The relationship between molecular expression of TIGAR protein and tumor angiogenesis was explored. The carbon flow and Extracellular acid change of the different expression of TIGAR state change of tumor cells was determined by isotope labeled glucose flow analysis techology and XF24 Extracellular Flux Analyzer for Cellular Bioenergetics. It is was explored that correlation and molecular mechanism between the changes of expression of TIGAR protein and cell acid environment. Establishment of the theoretical system between targeting tumor cells glycolysis level and inhibit angiogenesis induced migration, which lays a theoretical foundation for the clinical application of combined anti-metabolism drugs and anti angiogenesis drugs in the treatment of cancer.

英文关键词： molecular imaging;glucose metabolism;metastasis