Effect of gonadotropin-releasing hormone-Ⅰ agonist and gonadotropin-releasing hormone-Ⅱ on endometrial carcinoma cell lines with different states of PTEN
10.3760/cma.j.issn.0529-567x.2009.01.012
- VernacularTitle:促性腺激素释放激素Ⅰ型激动剂和Ⅱ型对不同PTEN基因表达状态子宫内膜癌细胞的作用
- Author:
Lijun ZHAO
;
Lihui WEI
;
Xiaoping LI
;
Jianliu WANG
- Publication Type:Journal Article
- Keywords:
Endometrial neoplasms;
PTEN phosphohydrolase;
Gonadotropin-releasing hormone;
Triptorelin;
Estradiol
- From:
Chinese Journal of Obstetrics and Gynecology
2009;44(1):45-49
- CountryChina
- Language:Chinese
-
Abstract:
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 10-5 mol/L) or GnRH-Ⅱ (10-11 to 10-5 mol/L). Thirty min later, serine/threonine protein kinase(Akt) and extracellular signal-regulated 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 (MTT) 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 dose-dependent 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 EBK1/2 activity in the endometrial carcinoma cells. 17β-E2 counteracted the effect of triptorelin and GnRH-Ⅱ on the endometrial carcinoma cells (P<0.01, P <0. 05). Conclusion Triptorelin 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.
