绒癌的发生与胎盘滋养层干细胞的异常分化有关，20%的患者因化疗耐药成为临床治疗难点。研究发现miR-200家族是参与肿瘤上皮-间质转化(EMT)及耐药的通用管家，与干细胞分化密切相关。我们前期研究发现具有干细胞特性的细胞滋养细胞合体化障碍与绒癌耐药相关。绒癌细胞中与干细胞分化密切相关的Notch信号通路表达下降，缺氧条件可激活Notch促进绒癌细胞发生EMT，但miR-200家族在绒癌中受Notch通路状态影响调控滋养细胞EMT导致其耐药的机制尚不清楚。本研究拟以绒癌细胞株、移植瘤动物模型及临床组织、血清标本为研究对象，在体内、外水平采用基因转染技术稳定控制Notch通路活性，观察绒癌细胞株EMT、化疗敏感性、miRNA表达谱等变化，同时采用pre-miRNA及miRNA Sponge、双荧光素酶报告基因等分子技术探索miR-200家族在此过程中的分子机制，为耐药绒癌患者的治疗提供新线索。

Choriocarcinoma (CC) is the most malignant trophoblastic tumor, which derives from the abnormal differentiation of placental trophoblast stem cells. CC is sensitive to chemotherapy, but all most 20% of CC patients are still resistant to chemotherapy, which is the treatment dilemma in clinics. Notch signaling pathway, which closely related to cell differentiation, is also involved in the regulation of epithelial-mesenchymal transition (EMT) and drug chemo-sensitivity in a variety of tumor cells. Recent studies have shown that as a versatile watchdog in carcinogenesis, EMT and drug resistance, miR-200 family is also closely involved in the differentiation of stem cells. Our previous study has found that EMT is associated with the differentiation of trophoblast cells, and hypoxia conditions can promote EMT in choriocarcinoma cells by activating Notch signaling pathway. However, the mechanism of microRNA-200 family in regulation of EMT of trophoblast cell controlled by the Notch signal pathway in choriocarcinoma remains unclear. In this study, choriocarcinoma cell lines, animal models in vivo, clinical tissues and serum samples from patients are used as research projects, and the activity of Notch pathway will be controlled by gene transfection technique of overexpression and knockout, then the biological behavior, EMT, chemo-sensitivity and miRNA-200 expression profile in transfected choriocarcinoma cell lines and animal model will be evaluated. Furthermore, by using pre-miRNA and miRNA sponge technology, the mechanism of miR-200 family to regulate EMT-mediated by Notch signal pathway in this process will be explored deeply, hoping to provide a new clue for the diagnosis and treatment of drug-resistant choriocarcinoma.