7-二氟甲氧基-5,4'-二-正辛烷氧基金雀异黄素下调FOXM1抑制卵巢癌细胞生长  

Growth inhibition by 7-difluoromethoxyl-5,4’-di-n-octyl genistein via the inactivation of FOXM1 in ovarian cancer cells

作　　者：唐爱琼[1] 曹晓正 全梅芳[2] 刘飞[2] 向红琳[2] 

机构地区：[1]湖南省妇幼保健院,湖南长沙410008 [2]湖南师范大学医学院,湖南长沙410013

出　　处：《湖南师范大学学报（医学版）》2012年第4期6-9,13,共5页Journal of Hunan Normal University(Medical Sciences)

基　　金：国家自然科学基金面上项目(8117235)

摘　　要：目的:研究新型金雀异黄素衍生物7-二氟甲氧基-5,4'-二正辛烷氧基金雀异黄素(DFOG)抑制人卵巢癌SKOV3细胞生长作用及其分子机制。方法:采用MTT法和集落形成法分析金雀异黄素以及DFOG对人卵巢癌SKOV3细胞生长的抑制作用。采用多种分子生物学技术如RT-PCR、Western blot、siRNA以及cDNA转染等探索分子机制。结果:金雀异黄素的9种衍生物抑制SKOV3细胞增殖活性作用均比金雀异黄素强,其中DFOG的抑制作用最强。DFOG和金雀异黄素导致SKOV3细胞生长抑制。DFOG能有效降低FOXM1和它下游基因(CDC25B,cyclin B)表达,上调p27KIP1表达。siRNA下调FOXM1后,再用DFOG处理,增强DFOG的细胞生长抑制作用。cDNA转染上调FOXM1能削弱DFOG诱导细胞生长抑制作用。结论:FOXM1介导金雀异黄素和DFOG抑制卵巢癌细胞生长作用,提示FOXM1可能成为治疗人卵巢癌的一个新靶标。Objective To examine the antitumor effects of 7-difluoromethoxyl-5,4’-di-n-octylgenistein(DFOG),a novel synthetic genistein derivative,on human ovarian cancer cells and its molecular mechanism. Methods Human ovarian cancer SKOV3 cells were cultured in vitro.The growth inhibitory effects of genistein and DFOG were examined using MTT assay and clonogenic assay.Multiple molecular techniques,such as RTPCR,Western blot analysis,siRNA and cDNA transfection were used to explore the molecular mechanism. Results Nine of genistein derivatives had more effective antitumor activity than genistein,among these derivatives,DFOG showed the strongest activity against SKOV3 cells in vitro.DFOG and genistein inhibited the growth of SKOV3 cells.DFOG caused attenuation of FoxM1 and its downstream genes,such as CDC25B,cyclin B,and increased p27KIP1.Down-regulation of FOXM1 by siRNA followed by DFOG treatment resulted in enhanced cell growth inhibition.Up-regulation of FoxM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition.Conclusion Our results show that the molecular role of FOXM1 in mediating the biological effects of genistein and DFOG in human ovarian cancer cells,suggesting that FoxM1 could be a novel target for the treatment of human ovarian cancer.

关 键 词：卵巢癌 金雀异黄素 7-二氟甲氧基-5 4’-二正辛烷氧基金雀异黄素 FOXM1 

分 类 号：R737.31[医药卫生—肿瘤]