放射诱导卵巢癌非肿瘤干细胞（NSCCs）可塑性变化机制研究

项目名称： 放射诱导卵巢癌非肿瘤干细胞（NSCCs）可塑性变化机制研究

项目编号： No.11305204

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 吴瑾华

作者单位： 中国科学院合肥物质科学研究院

项目金额： 30万元

中文摘要： 放射治疗是癌症三大治疗手段之一，但有研究报道放疗在部分杀死癌细胞同时，会诱导非肿瘤干细胞转化为肿瘤干细胞，导致肿瘤复发。非肿瘤干细胞去分化，即可塑性，在非肿瘤干细胞转化为肿瘤干细胞的过程中起到重要作用。本研究拟以卵巢癌细胞系为对象，在调查卵巢癌细胞系肿瘤干细胞/侧群细胞分布、优化标记蛋白组合检测标准和干性（stemness）基因表达模式的基础上，利用流式细胞分析术比较不同辐射源（X射线和γ射线）的辐照效应以及卵巢癌细胞系照射前后侧群细胞的比例变化；通过检测新生侧群细胞生长、抗药性、转移和干性基因表达水平，探明侧群细胞是否具备肿瘤干细胞的特性。本研究旨在探明射线对非肿瘤干细胞可塑性的影响以及诱导非肿瘤干细胞转化为肿瘤干细胞的可能性，为放疗在癌症治疗中的应用策略提供依据。

中文关键词： 卵巢癌；肺癌；放射治疗；侧群细胞；

英文摘要： Radiotherapy is one of the three major cancer therapeutics. However studies have shown that in addition to killing cancer cells, radiation therapy transforms non-stem cancer cells (NSCCs) into cancer stem cells through dedifferentiation. The NSCCs plasticity (ability to de-differentiate) has been suggested to play a major role in tumor recurrence. In this study, we are planning to use established ovarian cancer cell lines as a models to investigate the possible effect of radiation on the dedifferentiation of NSCCs. Several studies have established cell surface markers and gene expression profiles for ovarian cancer cell stem cell/ side population (SP). We would use florescence assisted cell sorting (FACS) to isolate NSCC population from heterogeneous cancer cells and irradiate them with X-ray and γ-radiation. Based on gene signatures and cell surface markers the efficiency as well as the change in distribution of the SP cells post irradiation would be determined. A detailed study on the stemness genes expression patterns along with characterization of proliferation, motility and cytokines expression patterns of the newly formed SP cells would further indicates the aggressiveness of the dedifferentiated population. Furthermore standard chemotherapeutics would be used to check for increased resistance of the SP ce

英文关键词： ovarian cancer；lung cancer；radiation therapy；sub-population cells；