糖皮质激素对人卵巢癌HO-8910细胞TβR-Ⅱ的上调作用

Glucocorticoid up-regulated TβR-Ⅱ in ovarian cancer HO-8910 cells

目的 :研究转化生长因子 β1 (transforminggrowthfactor β1 ,TGF β1 )通路是否参与人工合成糖皮质激素地塞米松 (dexamethasone ,Dex)对人卵巢癌细胞系HO 891 0增殖抑制的过程。方法 :分别采用细胞计数和流式细胞分析方法检测细胞增殖和细胞周期分布 ;定量RT PCR、ELISA和 (或 )免疫细胞化学检测TGF β1及其受体TβR Ⅰ和TβR Ⅱ的表达水平。 结果 :Dex可引起HO 891 0细胞周期G0 G1 期进展停滞 ,并可明显上调TβR ⅡmRNA的表达 ,且具有浓度依赖性特点 ,Dex处理细胞 8小时作用最强 ,此时 1 0 -7mol L浓度组TβR ⅡmRNA水平比对照组升高约 1 .4倍 (P <0 .0 1 ) ;TβR Ⅱ的蛋白表达水平也增加。糖皮质激素受体 (glucocorticoidreceptor,GR)阻断剂RU486能够逆转这些作用。而Dex对TGFβ1mRNA表达和蛋白分泌、对TβR ⅠmRNA的表达均没有调节作用。 结论 :Dex抑制HO 891 0细胞增殖的机制可能包括上调TβR Ⅱ的表达 。

Purpose:To investigate whether transforming growth factor β1 (TGF β1) pathway is involved in the mechanism of dexamethasone (Dex) mediated proliferation inhibition in ovarian cancer cell line HO 8910.Methods:To analyse cell proliferation and cell cycle distribution by cell counts and flow cytometric analysis, respectively ; to determine the expression levels of TGF β1 and its two receptors, TβR Ⅰ and TβR Ⅱ , by quantative RT PCR, ELISA and(or) immunocytochemistry methods.Results:Dex induced a G 0 /G 1 cell cycle arrest in HO 8910 cells, and it up regulated TβR Ⅱ expression in a concentration dependent manner.The level of TβR Ⅱ mRNA was the highest after treatment with Dex for 8 hours, with 1.4 fold more than that of control at concentration of 10 -7 mol/L ( P <0.01). The expression of TβR Ⅱ protein was also enhanced. RU486, an antagonist of glucocorticoid receptor(GR), could reverse these effects. Moreover, Dex did not affect the expression of TGF β1 or TβR Ⅰ mRNA , nor the secretion of TGF β1 protein.Conclusions:Up regulation of TβR Ⅱ mediated by GR might take part in the course of Dex induced inhibition of HO 8910 cell proliferation.