DAPT抑制妊娠滋养细胞肿瘤Notch信号通路对细胞增殖和EMT影响的研究  

A study on the role of notch signaling pathway in gestational trophoblastic tumor

作　　者：周园园[1] 薛艳[1] 田泉[1] 安瑞芳[1] 

机构地区：[1]西安交通大学医学院第一附属医院妇产科,西安710061

出　　处：《现代妇产科进展》2015年第5期330-333,共4页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目(No:81172489)

摘　　要：目的:探讨Notch信号通路在人妊娠滋养细胞肿瘤发生发展过程中的重要作用,及其与EMT之间的关系。方法:采用γ-分泌酶抑制剂DAPT处理JAR和JEG-3两种人绒毛膜癌细胞株,MTT法检测两种细胞株的增殖情况,q PCR法检测Notch1 mRNA表达。Western blot法检测DAPT阻断Notch信号通路后JAR细胞中EMT相关蛋白E-cad的表达情况。结果:DAPT能抑制JEG-3、JAR细胞生长,10μmol/L和15μmol/L DAPT作用48h开始分别抑制JEG-3和JAR细胞生长(P<0.05),且抑制作用呈时间和浓度依赖关系。JEG-3细胞中,1μmol/L和10μmol/L DAPT作用组中Notch1 mRNA表达下调,两组比较差异无统计学意义(P>0.05);JAR细胞中,10μmol/L和15μmol/L DAPT作用组中Notch1 mRNA表达下调,两组比较差异有统计学意义(P<0.05)。DAPT能上调JAR细胞中E-cad表达。结论:Notch信号通路和EMT与妊娠滋养细胞肿瘤的发生发展有关;γ-分泌酶抑制剂DAPT或可成为妊娠滋养细胞肿瘤治疗的一个新靶点。Objective：To study the significance of Notch signaling pathway in the development of gestational trophoblastic tumor and the relationship between EMT. Methods：The choriocarcinoma cell lines JAR and JEG-3 were treated with gamma-secretase inhibitor（DAPT）. Using MTT assay to examine the activity of the two cell lines and evaluate the infuluence on the proliferation in JAR and JEG-3 cells of DAPT. q PCR was performed to assess mRNA expression of Notch1. In addition,EMT related protein E-cadherin was detected by Western blot. Results：DAPT could inhibit JEG-3 cells and JAR cells growth,down-regulate the expression of Notch1 mRNA,and up-regulate the expression of E-cadherin in JAR cells. Conclusions：Notch sigaling pathway and EMT may be associated with the development of gestational trophoblastic tumor. DAPT may be a potential target of new therapeutic investigation in gestational trophoblastic tumor.

关 键 词：妊娠滋养细胞肿瘤 NOTCH信号通路 EMT Γ-分泌酶抑制剂 

分 类 号：R711.1[医药卫生—妇产科学]