卵泡刺激素(FSH)对卵巢癌HEY细胞系Notch通路及转录因子Snail表达的影响  

Follicle stimulating hormone(FSH) promotes Notch signaling and expression of Snail in ovarian cancer cell line HEY

作　　者：刘姝蓉[1] 姚晔俪[2] 贾罗琦[1] 陈奇[1] 丁景新[1] 华克勤[1] 丰有吉[3] 

机构地区：[1]复旦大学附属妇产科医院妇科,上海200011 [2]浙江大学附属妇产科医院妇产科,杭州310006 [3]上海交通大学附属第一人民医院妇产科,上海200080

出　　处：《复旦学报（医学版）》2013年第4期385-389,共5页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金项目(81072130;30872755);上海市卫生局青年科研基金项目(2008Y008)~~

摘　　要：目的研究卵泡刺激素(follicle stimulating hormone,FSH)体外对卵巢癌HEY细胞系Notch通路上Notch1胞内段蛋白(N1ICD)、转录因子CSL与靶基因表达以及对转录因子Snail家族的调节作用,以探讨FSH促进卵巢癌侵袭的可能机制。方法体外培养卵巢癌HEY细胞系,设PBS对照组和FSH 40mU/mL实验组,改良的Boyden小室检测两组细胞侵袭力,Western blot检测两组N1ICD、CSL、Snail、Slug蛋白表达,RT-PCR检测HEY-1、HEY-2、HES-1mRNA表达。结果 FSH 40mIU/mL可显著增强卵巢癌HEY细胞系的侵袭能力(P=0.001)。相比于对照组,实验组FSH 40mIU/mL作用24h后N1ICD和CSL蛋白表达显著上升(P=0.001,P=0.028)。FSH 40mIU/mL作用后18～24hHEY-1mRNA的表达增加,作用24h时HEY-2mRNA的表达增加。而FSH作用后HES-1mRNA水平无明显变化。FSH 40mIU/mL作用24h后,相比于对照组Snail蛋白表达显著上升(P=0.009),而Slug蛋白的表达无显著变化(P>0.05)。结论 FSH可能激活Notch1信号通路和Snail转录因子,进而促进卵巢癌细胞的侵袭能力。Objective To assess the effect of follicle stimulating hormone （FSH） on Notch1 intracellular domain （NIICD）, transcriptional factor CSL, Notch1 target gene and Snail family of ovarian cancer cell line HEY,and to investigate the possible mechanism by which FSH stimulates the invasion of the ovarian cancer. Methods Ovarian cancer cell line HEY was cultured and treated by 40 mIU/mL FSH or PBS as control. The cell invasion assay was performed by using the modified Boyden chambers. NIICD, CSL, Snail and Slug protein expression was detected by Western blot, and HEY-l, HEY-2 and HES-1 mRNA expression was measured by RT-PCR. Results 40 mIU/mL FSH significantly promoted the invasion of the HEY cells （P = 0. 001）. After treated with FSH for 24 hours,the expression of NIICD and CSL of HEY cells was significantly elevated compared with the control group （P = 0. 001, P = 0. 028）. RT-PCR showed that the expression of HEY-I mRNA was elevated after treated with FSH for 18 to 24 hours, and that the expression of HEY-2 mRNA was elevated after treated with FSH for 24 hours,while the expression of HES-1 mRNA was not changed after treated with FSH. After treated with FSH for 24 hours,the expression of Snail of HEY cells was significantly elevated compared with the control group （P = 0. 009） ,but the expression of Slug was not changed （P〉0.05）. Conclusions FSH activated Notchl signaling and transcriptional factor Snail, and thus promoted the invasion of ovarian cancer cells.

关 键 词：卵泡刺激素(FSH) 卵巢癌 Notch1 CSL Snail 

分 类 号：R737.3[医药卫生—肿瘤]