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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenocarcinoma, Clear Cell / drug therapy*
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Adenocarcinoma, Clear Cell / pathology
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Animals
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Antineoplastic Agents, Hormonal / pharmacology
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Antineoplastic Agents, Hormonal / therapeutic use*
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Bombesin / analogs & derivatives
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Bombesin / antagonists & inhibitors*
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Bombesin / pharmacology
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Bombesin / therapeutic use*
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ErbB Receptors / biosynthesis
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ErbB Receptors / genetics
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Female
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Gastrin-Releasing Peptide / antagonists & inhibitors*
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Gene Expression Regulation, Neoplastic / drug effects
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Gonadotropin-Releasing Hormone / analogs & derivatives
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Gonadotropin-Releasing Hormone / antagonists & inhibitors*
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Gonadotropin-Releasing Hormone / pharmacology
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Gonadotropin-Releasing Hormone / therapeutic use*
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Humans
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Luteinizing Hormone / blood
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Mice
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Mice, Nude
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / pathology
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Peptide Fragments / pharmacology
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Peptide Fragments / therapeutic use*
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RNA, Messenger / biosynthesis
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RNA, Neoplasm / biosynthesis
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Receptors, Bombesin / biosynthesis
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Receptors, Bombesin / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Specific Pathogen-Free Organisms
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents, Hormonal
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Neoplasm Proteins
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Peptide Fragments
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Bombesin
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bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-
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Gonadotropin-Releasing Hormone
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Gastrin-Releasing Peptide
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Luteinizing Hormone
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ErbB Receptors
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cetrorelix
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Bombesin