应激微环境与p53氧化还原修饰对肝肿瘤细胞能量代谢平衡的调控作用研究

项目名称： 应激微环境与p53氧化还原修饰对肝肿瘤细胞能量代谢平衡的调控作用研究

项目编号： No.31270901

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 施冬云

作者单位： 复旦大学

项目金额： 80万元

中文摘要： 肿瘤因快速生长需求而具特异的能量代谢及氧化还原状态。近期研究发现p53具有调节能量代谢的新功能，但其机制尚不明。课题组原承担的国家自然科学基金重点项目已证实，肿瘤细胞生长可被活性氧（ROS）调控并具依赖性，并知ROS与p53关系密切，包括可氧化修饰p53，但它们之间相互作用及是否协同参于能量代谢平衡的调节尚不清楚。根据原来的工作基础，发现不同活性氧对肿瘤细胞生长可产生不同效果，结合"SCIENCE"最新报道活性氧可以氧化修饰代谢通路的关键酶蛋白，启示特定活性氧也可能通过对p53氧化修饰而调控肿瘤的能量代谢平衡。如能阐明其机制，不仅理论上有重要价值，对肿瘤防治也将具有深远意义。故拟建立不同转染细胞株及内外源不同氧化还原微环境，采用分子生物学及ESR波谱技术等多学科手段，深入探究活性氧应激与p53修饰和新调节功能之间的内在联系，以能找到对肿瘤能量代谢平衡的敏感调控点。

中文关键词： ROS；氧化还原阈值；线粒体功能；糖酵解；能量代谢

英文摘要： Tumor cells have specific energy metabolism and redox status in order to meet their rapid growth. The recent researches have shown that p53 has a new role in regulating energy metabolism, but its mechanism is still unclear. Our previous project which was funded by the Key Program of National Natural Science Foundation of China has proved that the tumor cells can be regulated by ROS, and the tumor cells' growth relies on a certain level of ROS. It is known that ROS and p53 have an intimate relationship. ROS can oxidize and modify p53, however it is unknown whether they interact and cooperate with each other to participate in regulating the balance of energy metabolism. According to our previous works that different species of ROS have different impacts on tumor cells' growth, and combining with the latest results published on "SCIENCE" that ROS can oxidize and modify the key enzyme involved in the metabolic pathway, it suggests that ROS may regulate p53 by oxidative modification and thus regulate the energy metabolism balance of tumor. Understanding its mechanism will have important significance not only in theory but also in cancer prevention and treatment. Therefore, we plan to establish the various cell lines and different endogenously and exogenously redox microenvironments, we will explore the internal relat

英文关键词： ROS；redox threshold；mitochondrial function；glycolysis；energy metabolism