TGF-β/Akt/Smad介导的上皮间质转化在电离辐射增加肿瘤细胞转移潜能中的作用

项目名称： TGF-β/Akt/Smad介导的上皮间质转化在电离辐射增加肿瘤细胞转移潜能中的作用

项目编号： No.31200633

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 周咏春

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 转移是肿瘤治疗，包括放射治疗失败的主要原因之一，放疗是否能直接促进肿瘤细胞发生转移，尚未见报道。我们前期发现，单次常规分割剂量的电离辐射可以通过诱导离体肿瘤细胞发生上皮间质转化（EMT）进而增加其转移潜能，同时，细胞转化生长因子-β（TGF-β）的表达也明显升高。然而，放射治疗是连续几周的多次照射过程，该模式下肿瘤细胞EMT的变化规律如何，目前尚不清楚。此外，作为EMT的重要诱导因子，TGF-β在电离辐射诱导的EMT中扮演什么角色，其下游信号又是如何传递和发生交互作用的，均需进一步阐明。本课题将模拟临床放疗参数，照射不同组织来源的肿瘤细胞，从形态学、标志物和功能学角度观察EMT的变化规律，再运用免疫学方法检测TGF-β及下游Smad、Akt信号分子的改变，并通过多种干预手段分析它们的作用及相互关系。本研究将为明确放疗和肿瘤转移的关系及机制提供实验基础，为相关分子靶向药物的研发提供理论依据。

中文关键词： 电离辐射；肿瘤转移；上皮间质转化；转化生长因子-β；放射治疗

英文摘要： Metastasis is one of the main reasons for the failure of cancer therapy, and it is also involved in radiotherapy. It has not been reported whether radiotherapy induce the metastasis of cancer cells directly. In previous studies, we concluded that ionizing radiation could promote metastatic potential of cancer cells through epithelial-mesenchymal transition (EMT), and the expressions of transforming growth factor-beta (TGF-β) were increased remarkably. However, cancer cells need to be irradiated many times continuously for several weeks in the course of radiotherapy, and the changes of EMT are still unknown in this process. Moreover, as an important trigger of EMT, what role of TGF-β in radiation-incuced EMT, and what about the transduction and crosstalk of its downstream signal, both of which are need to be clarified. In further study, some cancer cell lines originated from different human organs will be irradiated with X ray which come from conventional fraction-dose and times in clinical radiotherapy, and the changes associated with EMT will be observed, including morphology, EMT markers and functional indexes. Then the expressions of TGF-β and its downstream molecules related with Smad and Akt signals will be detected by immunological methods, and the effects and relationship between them in radiation induced

英文关键词： Ionizing Radiation (IR)；Tumor Metastasis；Epithelial-Mesenchymal Transition (EMT)；Transforming Growth Factor-beta (TGF-β)；Radiotherapy