地塞米松和TGFβ_1对人卵巢癌HO-8910细胞中PAI-1表达的影响  

Effect of dexamethasone and transforming growth factor β_1 on expression of plasminogen activator inhibitor-1 in human ovarian cancer cell line HO-8910

作　　者：王雁[1] 曹冬梅[1] 王燕[1] 闫亚敏[1] 卢建[1] 

机构地区：[1]第二军医大学基础部病理生理学教研室,上海200433

出　　处：《第二军医大学学报》2010年第1期7-11,共5页Academic Journal of Second Military Medical University

摘　　要：目的观察地塞米松(Dex)和转化生长因子β1(TGFβ1)对人卵巢癌HO-8910细胞中Ⅰ型纤溶酶原激活物抑制剂(PAI-1)表达的影响,探讨其在卵巢癌的发生发展中可能发挥的作用。方法将HO-8910细胞分别用TGFβ1(0.01～10ng/ml)和Dex(100nmol/L)单独或联合处理不同时间后,用实时定量PCR和蛋白质印迹法检测PAI-1mRNA和蛋白表达的变化;用放线菌素D阻断新的mRNA合成,检测PAI-1mRNA的稳定性。结果HO-8910细胞中,TGFβ1能以时间和浓度依赖性的方式上调PAI-1mRNA的表达,最高可上调3.75倍(P<0.01);Dex也能上调PAI-1mRNA的表达,最高为1.65倍(P<0.01);Dex和TGFβ1两者联合作用4h,可上调PAI-1mRNA12.7倍(P<0.01),远大于两者单独作用之和,两者联合处理对PAI-1蛋白的上调作用也大于两者单独作用;Dex和TGFβ1单独及联合作用均不影响PAI-1mRNA的稳定性。结论Dex和TGFβ1单独均能上调HO-8910细胞中PAI-1的表达,联用对PAI-1上调有协同作用,该协同作用不是通过增强PAI-1mRNA的稳定性,而是通过它们在转录水平的作用实现的。Objective To observe the effect of dexamethasone （ Dex） and transforming growth factor β1 （ TGFβ1） on the expression of plasminogen activator inhibitor -1 （ PAI -1） in human ovarian cancer cell line HO -8910,and to explore its role in the development and progression of human ovarian cancer. Methods Human HO -8910 cells were treated with Dex（ 100 nmol/L） or TGFβ1（ 0. 01 -10 ng/ml） or both for different time periods,then the expression of PAI -1 mRNA and protein was examined by real-time PCR and Western blotting analysis. Act D was used to inhibit the synthesis of new mRNA so as to evaluate the stability of PAI -1 mRNA. Results TGFβ1 up-regulated PAI -1 mRNA expression in HO -8910 cells in a time-and dose-dependent manner,with the highest increase being 3. 75 folds （ P 〈 0. 01） ; Dex also up-regulated PAI -1 mRNA expression,with the highest increase being 1. 65 folds （ P 〈 0. 01）. Dex combined with TGFβ1 markedly up-regulated PAI -1 mRNA level,with the highest increase being 12. 7 .folds （ P 〈 0. 01） ,which was greatly higher than the sum of Dex and TGFβ1. Dex combined with TGFβ1also greatly up-regulated the PAI -1 protein level compared with Dex or TGFβ1 alone. Dex,TGFβ1 or combination of them did not affect the stability of PAI -1 mRNA. Conclusion Both Dex and TGFβ1 can up -regulate the expression of PAI -1 in HO -8910 cells,and the combination of them can work synergistically to up-regulate PAI -1 expression. The synergistic effect occurs at the transcriptional level,and it is not due to enhenced stability of PAI -1 mRNA.

关 键 词：孵巢肿瘤 地塞米松 转化生长因子B 纤溶酶原激活物抑制物1 

分 类 号：R737.31[医药卫生—肿瘤]