Treatment with luteinizing-hormone-releasing hormone antagonist sb-75 decreases levels of epidermal growth-factor receptor and its messenger-RNA in ov-1063 human epithelial ovarian-cancer xenografts in nude-mice

The aim of this study was to investigate the effect of administration of LH-RH antagonist SB-75 and agonist [D-Trp(6)]LH-RH on receptors for epidermal growth factor (EGF) in OV-1063 human epithelial ovarian cancer. Female athymic nude mice bearing xenografts of OV-1063 human epithelial ovarian cancer were treated for 3 weeks with the modern LH-releasing hormone (LH-RH) antagonist [Ac-DNal(2)(1), D-Phe(4Cl)(2), D-Pal(3)(3), D-Cit(6), D-Ala(10)] LH-RH (SB-75, Cetrorelix), the agonist [D-Trp(6)]LH-RH, or bombesin/gastrin-releasing peptide antagonist RC-3095. SB-75 and [D-Trp(6)] LH-RH were injected s.c. at doses of 100 mu g/day, and RC-3095 was injected at a dose of 40 mu g/day. Tumor growth, as measured by percentage change in tumor volume, was significantly inhibited by the treatment with SB-75, but not by [D-Trp(6)] LH-RH or RC-3095. Treatment with SB-75 greatly decreased the levels of mRNA for EGF receptor and reduced the number of EGF binding sites on tumor membranes. Effects of SB-75 on EGF receptors might be related to inhibition of tumor growth. Our findings support the view that LH-RH antagonists such as SB-75 could be considered for possible hormonal therapy of epithelial ovarian cancer.