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

Abstract

We evaluated the effects of the bombesin/gastrin-releasing peptide (GRP) antagonist RC-3095, and the luteinizing hormone-releasing hormone (LH-RH) antagonist Cetrorelix, administered singly or in combination, on the growth of human ovarian carcinoma cell line ES-2, xenografted into nude mice. RC-3095 at a dose of 20 microg/day and Cetrorelix (100 microg/day), significantly reduced the volume of ES-2 tumors by 63.0% (P<0.01) and 38.0% (P<0.05) respectively, after 44 days of treatment, as compared with controls. The combination 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 analyses 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 treated with Cetrorelix and by 72.5% (P<0.05) in the group that received the combination of RC-3095 with Cetrorelix. Our results indicate that the bombesin antagonist RC-3095 and the LH-RH antagonist Cetrorelix inhibit effectively the growth of ES-2 ovarian cancers in nude mice. These antagonists and their combination could be considered for the therapy of patients with ovarian cancer.

• Authors: I Chatzistamou, A V Schally, K Szepeshazi, K Groot, F Hebert, J M Arencibia
• Journal: Cancer letters (Cancer Lett) Vol. 171 Issue 1 Pg. 37-45 (Sep 28 2001) ISSN: 0304-3835 [Print] Ireland
• PMID: 11485826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents, Hormonal
• Neoplasm Proteins
• Peptide Fragments
• RNA, Messenger
• RNA, Neoplasm
• Receptors, Bombesin
• bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-
• Gonadotropin-Releasing Hormone
• Gastrin-Releasing Peptide
• Luteinizing Hormone
• ErbB Receptors
• cetrorelix
• Bombesin

Topics

• Adenocarcinoma, Clear Cell (drug therapy, pathology)
• Animals
• Antineoplastic Agents, Hormonal (pharmacology, therapeutic use)
• Bombesin (analogs & derivatives, antagonists & inhibitors, pharmacology, therapeutic use)
• ErbB Receptors (biosynthesis, genetics)
• Female
• Gastrin-Releasing Peptide (antagonists & inhibitors)
• Gene Expression Regulation, Neoplastic (drug effects)
• Gonadotropin-Releasing Hormone (analogs & derivatives, antagonists & inhibitors, pharmacology, therapeutic use)
• Humans
• Luteinizing Hormone (blood)
• Mice
• Mice, Nude
• Neoplasm Proteins (biosynthesis, genetics)
• Ovarian Neoplasms (drug therapy, pathology)
• Peptide Fragments (pharmacology, therapeutic use)
• RNA, Messenger (biosynthesis)
• RNA, Neoplasm (biosynthesis)
• Receptors, Bombesin (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Specific Pathogen-Free Organisms
• Xenograft Model Antitumor Assays