Inhibition of growth of OV-1063 human epithelial ovarian cancers and c-jun and c-fos oncogene expression by bombesin antagonists

摘要

Receptors for bombesin are present on human ovarian cancers and bombesin-like peptides could function as growth factors in this carcinoma. Therefore, we investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonists RC-3940-II and RC-3095 on the growth of human ovarian carcinoma cell line OV-1063, xenografted into nude mice. Treatment with RC-3940-II at doses of 10 μg and 20 μg per day s.c. decreased tumour volume by 60.9% (PPP = 0.15). In comparison, luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix at a dose of 100 μg per day caused a 64.2% inhibition (Pjun and c-fos oncogenes in a time-dependent manner. Antagonist RC-3940-II inhibited the stimulatory effect of GRP(14–27) on c-jun and c-fos in vitro. In vivo, the levels of c-jun and c-fos mRNA in OV-1063 tumours were decreased by 43% (PP = 0.05) respectively, after treatment with RC-3940-II at 20 μg per day. Exposure of OV-1063, UCI-107 and ES-2 ovarian carcinoma cells to RC-3940-II at 1 μM concentration for 24 h in vitro, extended the latency period for the development of palpable tumours in nude mice. Our results indicate that antagonists of bombesin/GRP inhibit the growth of OV-1063 ovarian cancers by mechanisms that probably involve the downregulation of c-jun and c-fos proto-oncogenes. ? 2000 Cancer Research Campaign