DFOG抑制卵巢癌A2780细胞系球形成细胞自我更新与活化FoxO3a相关

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目的:研究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A2780细胞系球形成细胞自我更新及其作用机制。方法:体外培养A2780细胞,干细胞条件培养基悬浮培养扩增球形成细胞(sphere forming cells,SFCs)。Western blot分析SFCs的CD133和CD44蛋白及磷酸化FoxO3a蛋白表达水平;MTT法测定SFCs增殖活性;肿瘤球形成试验检测SFCs自我更新能力。结果:A2780细胞系SFCs具有自我更新能力。与亲本细胞相比,SFCs高表达CD133及CD44并具有更高的磷酸化FoxO3a蛋白表达水平。DFOG以浓度依赖的方式抑制SFCs增殖与自我更新,并下调SFCs中磷酸化FoxO3a蛋白水平。结论:DFOG抑制人卵巢癌A2780细胞系球形成细胞自我更新与其活化FoxO3a蛋白相关。 OBJECTIVE: To study the self-renewal effect of DFOG on human granulosa cells of human ovarian cancer cell line A2780 and its mechanism. Methods: A2780 cells were cultured in vitro and cultured in suspension culture medium containing stem cells in suspension medium to form sphere forming cells (SFCs). The expression of CD133 and CD44 protein and phosphorylated FoxO3a protein in SFCs were analyzed by Western blot. The proliferation activity of SFCs was determined by MTT assay. The ability of self-renewal of SFCs was detected by tumor spheroid formation assay. Results: The A2780 cell line SFCs has self-renewal ability. Compared with parental cells, SFCs overexpressed CD133 and CD44 and had higher levels of phosphorylated FoxO3a protein expression. DFOG inhibited the proliferation and self-renewal of SFCs in a concentration-dependent manner and down-regulated phosphorylated FoxO3a protein levels in SFCs. CONCLUSION: DFOG inhibits the self-renewal of spherical cells of A2780 human ovarian cancer cells by activating FoxO3a protein.
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