中文摘要：

目的探讨促性腺激素释放激素Ⅰ型（GnRH—Ⅰ）激动剂——曲普瑞林和GnRH—Ⅱ对不同PTEN基因表达状态的子宫内膜癌细胞的作用。方法不同浓度（10^-11、10^-9、10^-7、10^-5mol／L）的曲普瑞林和GnRH-Ⅱ分别作用于不同PTEN基因表达状态的3种子宫内膜癌细胞细胞系Ishikawa[PTEN基因表达阴性（-）]、Ishikawa—PTEN[PTEN基因表达阳性（＋）]、Ishikawa-neo[PTEN（-）]细胞后，应用四甲基偶氮唑蓝比色法、碘化丙啶染色流式细胞计数法、膜联蛋白染色流式细胞术检测内膜癌细胞增殖、细胞周期和细胞凋亡的变化；蛋白印迹法检测内膜癌细胞中蛋白激酶B（Akt）及细胞外信号调节激酶1／2（ERK1／2）的活化情况。在曲普瑞林和GnRH—Ⅱ作用的基础上，使用17β雌二醇（17β-E2，10^-8mol／L）和雌激素受体拮抗剂——ICI182780（10μmol／L）分别进行干预，再次检测上述指标的变化。结果不同浓度（10^-11、10^-9、10^-7、10^-5mol／L）的曲普瑞林及GnRH—Ⅱ作用后，3种细胞的增殖明显受到抑制（P〈0．01）；细胞凋亡率明显增加（P〈0．01或P〈0．05）；细胞生长减慢，G0／G1期细胞比例增多，G2／M期和S期细胞比例减少；上述作用均呈明显浓度依赖关系（JP〈0．01或P〈0．05）。曲普瑞林及GnRH-Ⅱ均可明显抑制Ishikawa、Ishikawa-neo细胞中Akt和ERK1／2的活化（P〈0．01）；而对Ishikawa—PTEN细胞中Akt和ERK1／2的活化无明显抑制作用（P〈0．05）。17β—E2可明显拮抗曲普瑞林和GnRH-Ⅱ的上述作用（P〈0．01或P〈0．05）。结论曲普瑞林和GnRH-Ⅱ可通过抑制Akt和ERK1／2的活化，促进子宫内膜癌细胞凋亡，并抑制细胞增殖，此作用呈明显浓度依赖关系，并与PTEN基因表达状态有关，且可被17β-E2拮抗。提示GnRH-Ⅰ激动剂可用于低雌激素表达子宫内膜癌患者的个体化内分泌治疗。

英文摘要：

Objective To study the effect of gonadotropin-releasing hormone-Ⅰ （GnRH-Ⅰ ） agonist triptorelin and gonadotropin-releasing hormone-Ⅱ （ GnRH-Ⅱ ） on human endometrial carcinoma with different states of PTEN. Methods The endometrial carcinoma cells （ Ishikawa, Ishikawa-PTEN, and Ishikawa-neo） were treated with different concentrations of triptorelin （ 10^-11 to 10^-2 mol/L） or GnRH-Ⅱ （10^-11 to 10^-5 mol/L）. Thirty min later, serine/threonine protein kinase （Akt） and extracellular signalregulated kinase （ ERK ） 1/2 activation were detected using western blot method. 48 h later, the cell proliferation, cell cycle and apoptosis were detected using methyl thiazolyl tetrazolium （MTF） and flow cytometry. 17β-estradiol （17β-E2, 10^-8 mol/L） or the specific estrogen receptor （ER） antagonist, ICI182780I （10^-6 mol/L） was added. After using the two drugs： triptorelin or GnRH-Ⅱ , the above parameters were detected again. Results After treated with different concentrations （ 10^-11, 10^-9, 10^-7, 10^-5 mol/L） of triptorelin and GnRH-Ⅱ , the cell growth was slowed, the percentage of G0/G1 phase cells increased, the percentage of G2/M and S phase cells decreased and the apoptosis rate increased in a dosedependent manner （P 〈 0.01, P 〈 0. 05）. These changes were more obvious in Ishikawa. The apoptosis rate induced by GnRH-Ⅱ was higher than that by the same concentration of triptorelin in the three cell lines. Triptorelin and GnRH-Ⅱ inhibited the Akt and ERK1/2 activity in the endometrial carcinoma cells. 17β-E2 counteracted the effect of triptorelin and GnRH-Ⅱ on the endometrial carcinoma ceils （ P 〈 0. 01, P 〈 0.05）. Conclusion Triptorehn and GnRH- Ⅱ can promote apoptosis rate of endometrial carcinoma cells and inhibit cell proliferation in a dose-dependent manner which may be caused by ERK1/2 and Akt activity inhibition, and is related to the status of PTEN and could be offset by 17β-E2.