蛋白磷酸酶2A参与孕激素对子宫内膜上皮细胞增殖的负调控作用

目的探讨蛋白磷酸酶2A(protein phosphatase 2A,PP2A)是否参与孕激素对子宫内膜上皮细胞增殖的负调控作用,以进一步揭示孕激素作用的分子机制。方法分离培养原代小鼠子宫内膜上皮细胞,在细胞生长汇合时将其分为4组:以1μmol/L孕激素为对照组(P4组),其他3组分别给予1μmol/L孕激素和5nmol/L、10nmol/L、20nmol/L 3种不同剂量的PP2A抑制剂冈田酸(OA)作为实验组,分别为A、B和C组。各组细胞在上述实验因素作用24h后,采用流式细胞术检测细胞周期各时相分布的细胞百分数。结果与P4组相比,A组分布在细胞周期各时相的细胞百分数差异没有统计学意义;B组处于G1期和G2/M期的细胞百分数降低,而S期的细胞百分数增加;C组处于G1期和S期的细胞百分数增加,但G2/M期细胞百分数降低(P均<0.05)。结论适当剂量PP2A抑制剂OA可明显解除孕激素对子宫内膜上皮细胞增殖的抑制作用,使细胞周期进程加快,从而证实PP2A参与了孕激素对子宫内膜上皮细胞增殖的负调控作用。

PP2A is involved in the inhibitory effect of progesterone on proliferation of mouse endometrial epithelial cells

Objective To study the effect of protein phosphatase 2A（PP2A） in the negative regulation of progesterone on the proliferation of mouse endometrial epithelial cells（EECs）.Methods Mouse EECs were isolated and cultured in vitro,which were divided into four groups when they grown to confluence: control group（P₄） was treated with 1 μmol/L progesterone only,group A,B and C were treated respectively with 1 μmol/L progesterone and different concentrations of okadaic acid（5 nmol/L,10 nmol/L and 20 nmol/L）.After 24 h,the numbers of cells in different phases of the cell cycle were counted with flow cytometry.Results The effect of OA on mouse EECs was concentration-dependent.Compared with control group of P4,the change of cell cycle procession in group A was not obvious.Lower proportion of cells in G₁ and G₂/M phase and higher proportion of cells in S phase in group B,higher proportion of cells in G₁ and S phase and lower proportion of cells in G₂/M phase in group C were observed.Conclusion Adequate dose OA inhibiting PP2A could release the inhibitory effect of progesterone on proliferation of mouse EECs obviously,this suggested that PP2A was involved in the inhibitory effect of progesterone on proliferation of EECs by influencing the process of cell cycle.