Effekte und Wirksamkeitsvergleich verschiedener Gonadotropin-Releasing-Hormon (GnRH)-Analoga in gynäkologischen Karzinomzelllinien

The mode of action of the Gonadotropin-Releasing hormone (GnRH I and II) particularly at gynecological malignant tumors have been described by various investigators. The majority of human endometrial, ovarian and breast cancers express receptors for gonadotropin-releasing hormone (GnRH I and II). Their proliferation is time- and dose-dependently reduced by GnRH and its agonistic and antagonistic analogues. Recently, it was shown that two types of GnRH, GnRH-I and II; and their two types of receptors, type I and II, are expressed in endometrial and ovarian cancers. The two types are assumed to be part of the negative autocrine regulatory system and to have different effects on cell proliferation. The present study was performed in order to analyze the effect of different GnRH-agonsits and GnRH-antagonists on proliferation of ovarian, endometrial and breast cancer cells. There are different and partly contradictory data on the antiproliferative effects of GnRH analogues shown in the literature and these controversial results could be caused e.g. by different culture conditions or loss of GnRH-receptors in the cell lines. In order to avoid this potential bias, possible antiproliferative effects of six GnRH-analogues on cell proliferation were tested under identical trial conditions. The four GnRH-agonists triptorelin, goserelin, leuprorelin, buserelin and the two GnRH-antagonists ramorelix and cetrorelix were tested on four cell lines: one breast cancer cell line MCF-7, one endometrial cancer cell lline HEC-1A and two ovarian cancer cell lines EFO-21 and EFO-27. The cells were treated with increasing concentrations of the GnRH-analogues for five days.