罗格列酮对人子宫肌瘤细胞凋亡和雌激素受体表达的影响

Effect of rosiglitazone on cell apoptosis and expression of estrogen receptor in human uterine leiomyoma cells

目的:探讨罗格列酮对人子宫肌瘤细胞增殖和凋亡的影响及可能机制。方法:不同浓度的罗格列酮(10-8,10-7和10-6mol/L)处理原代培养的人子宫肌瘤细胞24,48和72h。用四甲基偶氮唑盐(methyl thiazolyl tet-razolium,MTT)法测定细胞生长曲线,用流式细胞术测定细胞凋亡率,采用放射免疫法测定培养液中雌二醇水平,实时定量PCR和Western免疫印迹分别检测雌激素受体α和β的表达。结果:罗格列酮(10-8,10-7和10-6mol/L)处理48和72h后以浓度和时间依赖的方式抑制了子宫肌瘤细胞的增殖,而罗格列酮(10-8,10-7和10-6mol/L)处理24h对子宫肌瘤细胞增殖的影响没有显著性。罗格列酮(10-8,10-7和10-6mol/L)处理72h以浓度依赖的方式促进了子宫肌瘤细胞的凋亡,同时以浓度依赖的方式降低了子宫肌瘤细胞雌二醇的分泌和雌激素受体α和βmRNA和蛋白的表达。结论:罗格列酮可抑制子宫肌瘤细胞增殖,促进其凋亡,其机制与罗格列酮降低子宫肌瘤细胞雌二醇的分泌和减少子宫肌瘤细胞中雌激素受体α和β的表达有关。

Objective To explore the effect of rosiglitazone（an agonist of PPARγ） on cell proliferation and apoptosis and the underlying mechanisms in human uterine leiomyoma cells.Methods Primary cultured human leimyoma cells were treated with different concentrations of rosiglitazone（10-8,10-7 and 10-6 mol/L） for 24,48 or 72 hours.Methyl thiazolyl tetrazolium（MTT） assay was used to detect the growth curve.The apoptosis rate of human leimyoma cells were measured by flow cytometry.The level of estradiol in culture medium was measured by radioimmunity assay.The mRNA and protein expression of estrogen receptor α and β in human leimyoma cells was measured by Real-time PCR and Western blot.Results The proliferations of human uterine leiomyoma cells were significantly inhibited by rosiglitazone treatment for 48 and 72 hours in a dose-dependent and time-dependent manner.There was no significant change in cell proliferation in groups treated by rosiglitazone for 24 hours at any concentration.The cellular apoptosis rates were obviously increased by rosiglitazone treatment for 72 hours in a dose-dependent manner.The levels of estradiol in culture medium were decreased by rosiglitazone treatment for 72 hours in a dose-dependent manner,accompanied by consistent changes of estrogen receptor（α and β） mRNA and protein expression.Conclusion Rosiglitazone inhibits the cells proliferation and promotes the cell apoptosis in human uterine leiomyoma cells,and the mechanism may be related to the decrease of estradiol secretion and estrogen receptor（α and β） expression.