EMT诱导肿瘤干细胞特性参与卵巢癌耐药的机制研究

项目名称： EMT诱导肿瘤干细胞特性参与卵巢癌耐药的机制研究

项目编号： No.81202055

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2

项目作者： 张丽瑞

作者单位： 西安交通大学

项目金额： 23万元

中文摘要： 转移及化疗耐药已成为卵巢癌患者治疗失败和死亡的主要原因。上皮间质转化(epithelial - mesenchymal transition, EMT)是肿瘤转移重要机制之一。最新的研究认为具有EMT和干细胞双重特性的癌细胞是肿瘤转移和耐药的关键，EMT和癌干细胞之间存在直接联系，但分子机制仍不清楚。本研究以上皮性卵巢癌细胞系为模型，通过EGF及TGFβ诱导EMT，观察EMT特征性改变、鉴定卵巢癌干细胞群的变化，并通过免疫荧光观察EMT及癌干细胞分子标志物的定位，观察化疗耐药，并检测包括HIF-1α、Twist、Zeb1、Snail和slug等EMT相关转录因子的表达；明确卵巢癌细胞发生EMT的同时是否可获得卵巢癌干细胞特性并参与耐药，阐明其可能的分子机制。通过RNA干扰靶向EMT相关转录因子的表达，并结合裸鼠体内移植瘤研究，探讨靶向EMT及卵巢癌干细胞信号通路的策略及对肿瘤转移及耐药的影

中文关键词： 卵巢癌；肿瘤干细胞；上皮间质转化；耐药；

英文摘要： Metastasis and chemo-resistance are the major reason which is responsible for the treatment failure and lead to the death of ovarian cancer patients. Epithelial-mesenchymal transition (EMT)) plays an important role in cancer metastasis. Advanced studies showed that cancer cells having double characteristic of EMT and stem cell line was the key point in tumor metastasis and chemo-resistance, EMT is closely related to cancer stem cells, the detailed molecular mechanism is not clear yet. In our present study, epithelial ovarian cell line is used as model, EMT is induced by EGF and TGF-β, investigate the change of EMT and identify the change of stem cells. The expression of transcription factors related to EMT, such as HIF-1α, Twist, Zeb1, Snail and Slug is detected. We try to elucidate if the ovarian cancer cells could obtain the character of cancer stem cells during cancer cells EMT, and whether this change participate in chemo-resistance. Based on the above findings, we try to explore the strategy using target EMT and disturb ovarian stem cells signal pathway to affect the cancer metastasis and chemo-resistance. The expression of EMT related transcription factors is knocked down by RNAi, and the EMT knock-down cell lines were implanted into nude mice to get the in vivo evidence.

英文关键词： ovarian cancer；cancer stem cell；epithelial - mesenchymal transition；chemoresistance；