Inhibition of growth of ES-2 human ovarian cancers by bombesin antagonist RC-3095, and luteinizing hormone-releasing hormone antagonist Cetrorelix

We evaluated the effects of the bombesin/gastrin-releasing peptide (GRP) an tagonist RC-3095, and the luteinizing hormone-releasing hormone (LH-RH) ant agonist Cetrorelix, administered singly or in combination, on the growth of human ovarian carcinoma cell line ES-2, xenografted into nude mice. RC-309 5 at a dose of 20 mug/day and Cetrorelix (100 mug/day), significantly reduc ed the volume of ES-2 tumors by 63.0% (P < 0.01) and 38.0% (P < 0.05) respe ctively, after 44 days of treatment, as compared with controls. The combina tion of RC-3095 with Cetrorelix inhibited the growth of ES-2 tumors by 66.2 % (P < 0.01). Serum levels of LH were significantly decreased in the groups treated with Cetrorelix alone and/or in combination with RC-3095. RT-PCR a nalyses revealed that the expression of mRNA for receptors of GRP (GRPR/BRS -1) and Neuromedin B (NMBR/BRS-2) on tumors was significantly decreased in all the treated groups. The expression of mRNA for epidermal growth factor receptors (EGFR) on tumors was reduced by 36.5% (P < 0.05) in the animals t reated with Cetrorelix and by 72.5% (P < 0.05) in the group that received t he combination of RC-3095 with Cetrorelix. Our results indicate that the bo mbesin antagonist RC-3095 and the LH-RH antagonist Cetrorelix inhibit effec tively the growth of ES-2 ovarian cancers in nude mice. These antagonists a nd their combination could be considered for the therapy of patients with o varian cancer. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.