GPER抑制剂PTX对雌激素作用下子宫内膜癌细胞增殖、凋亡的影响  

Effect of G protein-coupled receptor inhibitor on 17β-estradiol-induced proliferation and apoptosis in Ishikawa and HEC-1A cells

作　　者：乔玉环[1] 马秀英[1] 郭瑞霞[1] 李留霞[1] 葛新[1] 胡冬梅[1] 张燕彩[1] 

机构地区：[1]郑州大学第一附属医院妇产科,郑州450052

出　　处：《现代妇产科进展》2013年第1期13-16,共4页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金(No:81072124)

摘　　要：目的:探讨G蛋白偶联雌激素受体(GPER)抑制剂百日咳毒素(PTX)对17β-雌二醇(E2)作用下子宫内膜癌系ER阳性的Ishikawa及ER低表达的HEC-1A的细胞增殖、凋亡和细胞周期的影响,初步探讨阻断GPER介导的信号传导通路治疗子宫内膜癌的可行性。方法:选取对数生长的细胞随机分为空白对照组(不加任何试剂)、阴性对照组(加10-6mol/L E2)和实验组(10-6mol/L E2+PTX)。应用四甲基亚唑蓝(MTT)法、流式细胞术观察PTX对E2作用下的子宫内膜癌的细胞增殖、凋亡和细胞周期的影响。结果:(1)随着E2浓度的增加和作用时间的延长,子宫内膜癌Ishikawa细胞在490nm处光密度值增大。E2对Ishikawa细胞具有促增殖作用,且呈时间和浓度依赖性(P均<0.001),而对HEC-1A的细胞增殖作用不显著(P=0.393),各浓度之间差异均无统计学意义(P=0.137)。不同浓度E2作用48h后,Ishikawa细胞G0～G1期比例减少(P=0.001),S期比例增多(P=0.002),HEC-1A变化不显著。(2)随着PTX浓度增加及时间延长,两种细胞增殖能力逐渐下降并呈时间和浓度依赖性(P均<0.001);不同浓度PTX作用48h后,两种细胞的凋亡率、G0～G1比例均升高(P<0.001,P<0.05),S期比例在Ishikawa细胞无显著变化,在HEC-1A细胞降低,G2～M期比例在Ishikawa细胞降低,在HEC-1A细胞无显著变化。结论:PTX可以抑制E2对子宫内膜癌细胞的促增殖作用,促使其发生凋亡,抑制细胞周期进展。GPER介导的信号传导通路可能成为治疗子宫内膜癌的新靶点。Objective：To observe the influence of GPER inhibitor（PTX） on proliferation,cell cycle progression,and apoptosis of endometrial carcinoma cells stimulated by E2 and to explore the preliminary possible effect of PTX on treating endometrial carcinoma.Methods：The effects of PTX on E2-induced proliferation,apoptosis,and cell cycle distrubution of endometrial cancer cells were detected by monotetrazolium（MTT） assay and fluorescence-activated cell sorting technique.Results：（1）With increased concentrations of E2,the A490nm values of endometrial cancer cells increased gradually especially in Ishikawa cells in a time-dependent manner（P0.001）.Cell cycle distribution analysis revealed that percentage of Ishikawa cells at G0~G1 phase（F=34.078,P=0.001） decreased and percentage of S phase cells（P=0.002） increased significantly,whereas those of HEC-1A cells didn＇t show significant alteration.（2）Cotreatment of endometrial cancer cells with PTX,A490nm values of both cells decreased and also showed a time-dependent manner（P0.001）.The percentage of apoptotic cells increased significantly（P0.001）,the percentage of the cell population at G1 phase increased（P0.05） and the percentage of HEC-1A cells at S phase decreased（P=0.002）,whereas those of Ishikawa cell did not show significant alteration.The percentage of Ishikawa cells at G2~M phase increased and that of HEC-1A cells did not show significant alteration.Conclusion：Inhibition of GPER activity by PTX can inhibit Ishikawa cells proliferation induced by E2 and induce the endometrial cancer cell cycle arrest and cell apoptosis.GPER pathway presents an appealing therapeutic target on endometrial cancer.

关 键 词：子宫内膜肿瘤 受体 雌激素 rabGTP-结合蛋白质类 免疫组织化学 子宫内膜增生 病理学 临床 百日咳毒素 G蛋白偶联雌激素受体(GPER) 

分 类 号：R737.33[医药卫生—肿瘤]