摘要
背景与目的:子宫内膜癌发生发展与雌激素相关,芳香化酶抑制剂依西美坦可以竞争性灭活芳香化酶,降低雌激素水平,影响细胞的凋亡。本实验观察芳香化酶抑制剂依西美坦对子宫内膜癌细胞HHUA体外增殖凋亡活性及芳香化酶P450、雌激素受体(ER)、Survivin表达的影响,以确定依西美坦能否抑制子宫内膜癌的生长及其可能的作用机制。方法:应用四甲基偶氮唑蓝(MTT)法测定不同浓度依西美坦作用的子宫内膜癌HHUA细胞的吸光度(A);应用流式细胞仪(FCM)检测6×10-7mol/L依西美坦作用的子宫内膜癌HHUA细胞的凋亡率;采用免疫组化法检测依西美坦作用的子宫内膜癌HHUA细胞的ER、Survivin蛋白表达变化;应用RT-PCR法检测依西美坦作用的子宫内膜癌HHUA细胞P450、survivin mRNA转录。结果:不同浓度依西美坦对HHUA细胞体外增殖有抑制作用,增加细胞凋亡率。依西美坦显著下调ER、Survivin蛋白表达(P<0.05)。依西美坦浓度为6×10-7mol/L,培养72 h,HHUA细胞ER、Survivin蛋白表达染色评分分别为2.62±0.36和1.89±0.57,与对照组染色评分3.77±0.12和3.47±0.15比较,差异有显著性(P<0.05)。同样条件下,P450 mRNA光密度比值为1.67±0.15,对照组2.94±0.25,两者相比,差异有显著性(P<0.05)。survivin mRNA光密度比值为1.56±0.14,对照组2.57±0.21,两者相比,差异有显著性(P<0.05)。结论:依西美坦对子宫内膜癌细胞HHUA有增殖抑制和促凋亡作用,其抗肿瘤作用可能与降调P450、ER、survivin表达有关。
Background and purpose： The pathogenesis of endometrial carcinoma is associated with estrogen. Aromatase inhibitor exemestane can compete in the inhibition of the aromatase, reduce the quantity of estrogen. Our purpose was to investigate the effects of exemestane on the proliferation of human endometrial carcinoma cell line HHUA in vitro and its mechanism of action. Methods： The A values of the endometrial carcinoma cell HHUA treated with various concentrations （6 × 10^-5,6 × 10^-6, 6 × 10^ -7,6 × 10^-8, 6 × 10^-9moL/L） of exemestane were detected with the colorimetric 3-（4, 5-dimeth- ylthiazol-2-yl） -2, 5-diphenyhetrazolium bromide assay. The apoptosis rates of the HHUA cells treated with 6 × 10^-7moL/L of exemestane for 72 h were assessed by flow cytometry analysis technique. Immunohistochemical technique was used to determine the expression of ER, survivin proteins after treatment with 6 × 10^ -7mol/L of exemestane. The P450, survivin mRNA expressions were measured by RT-PCR after treatment with 6 × 10^-7mol/L of exemestane. Results： The A values of the endometrial carcinoma cells treated with 6 × 10^-8 6 × 10^-9mol/L of exemestane were similar to that of controls（ P 〉 0.05）, while those of the cells treated with 6 × 10^-5,6 × 10^-6,6 × 10^-7 mol/L of exemestane were significantly different from that of controls（ P 〈 0.05）. The apoptosis rates of exemestane group and control group were 32.4%, 5.3% respectively （ P 〈 0.05） . Immunohistochemical technique showed the expression of ER and survivin of exemestane group were significantly lower than that of control group（P 〈 0.05）. P450, survivin mRNA.levels of exemestane group were lower than that of control group（P 〈 0.05） . Conclusions： Exemestane can induce the apoptosis of endometrial carcinoma cell line HHUA in vitro. The anti-tumor effect was probably related to down-regulation of the expression of P450, ER and survivin.
出处
《中国癌症杂志》
CAS
CSCD
2007年第2期101-104,共4页
China Oncology
基金
国家自然科学基金资助(No:30640076)
关键词
依西美坦
子宫肿瘤
细胞凋亡
exemestane
endometrial carcinoma
apoptosis
