[Effect of gonadotropin-releasing hormone-I agonist and gonadotropin-releasing hormone-II on endometrial carcinoma cell lines with different states of PTEN].
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. 17beta-estradiol(17beta-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 ERK1/2 activity in the endometrial carcinoma cells. 17beta-E2 counteracted the effect of triptorelin and GnRH-II on the endometrial carcinoma cells (P < 0.01, P < 0.05).


CONCLUSIONS
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 17beta-E2.
Zhao
Li-jun
LJ
Department of Gynecology, Peking University People's Hospital, Beijing 100044, China.
Wei
Li-hui
LH
Li
Xiao-ping
XP
Wang
Jian-liu
JL
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human