Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor

Abstract

Background: The majority of human endometrial and ovarian cancer cell lines express receptors for GnRH. Their proliferation is time- and dose-dependently reduced by GnRH-I and its superagonistic analogues. Recently. we have demonstrated that, in human endometrial and ovarian cancer cell lines except for the ovarian cancer cell line EFO-27, the GnRH-I antagonist cetrorelix has antiproliferative effects comparable to those of GnRH-I agonists, indicating that the dichotomy between GnRH-I agonists and antagonists might not apply to the GnRH system in cancer cells. We were also able to show that the proliferation of human endometrial and ovarian cancer cells was dose- and time-dependently reduced by GnRH-II to a greater extent than by GnRH-I agonists. Objective: In this study we have assessed whether or not the antiproliferative effects of the GnRH-I antagonist cetrorelix in endometrial and ovarian cancer cells are mediated through the GnRH-I receptor. Methods: We analysed the antiproliferative effects of the GnRH-I agonist triptorelin, the GnRH-I antagonist cetrorelix and GnRH-II in a panel of endometrial and ovarian cancer cell lines expressing GnRH-I receptors, in the SK-OV-3 ovarian cancer cell line that does not express GnRH-I receptors, and in four GnRH-I receptor positive GnRH-I receptor knockout cell lines. Results: We found that, after knockout of the GnRH-I receptor, the antiproliferative effects of the GnRH-I agonist triptorelin were abrogated, whereas those of the GnRH-I antagonist cetrorelix and of GnRH-II persisted. Conclusions: These data suggest that, in endometrial and ovarian cancer cells, the antiproliferative effects of cetrorelix and of GnRH-II are not mediated through the GnRH-I receptor.