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

Ioulia Chatzistamou, Andrew V Schally, Karoly Szepeshazi, Kate Groot, Francine Hebert, Jose M. Arencibia

Research output: Contribution to journalArticle

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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 μg/day and Cetrorelix (100 μg/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.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalCancer Letters
Volume171
Issue number1
DOIs
StatePublished - Aug 28 2001
Externally publishedYes

Fingerprint

Hormone Antagonists
Bombesin
Gonadotropin-Releasing Hormone
Ovarian Neoplasms
Growth
Nude Mice
Neoplasms
Bombesin Receptors
Gastrin-Releasing Peptide
Messenger RNA
cetrorelix
Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-bombesin (6-14)
Carcinoma
Cell Line
Polymerase Chain Reaction
Therapeutics
Serum

Keywords

  • Bombesin/gastrin-releasing peptide
  • Cancer therapy
  • Luteinizing hormone-releasing hormone
  • Ovarian tumors

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Inhibition of growth of ES-2 human ovarian cancers by bombesin antagonist RC-3095, and luteinizing hormone-releasing hormone antagonist Cetrorelix. / Chatzistamou, Ioulia; Schally, Andrew V; Szepeshazi, Karoly; Groot, Kate; Hebert, Francine; Arencibia, Jose M.

In: Cancer Letters, Vol. 171, No. 1, 28.08.2001, p. 37-45.

Research output: Contribution to journalArticle

Chatzistamou, Ioulia ; Schally, Andrew V ; Szepeshazi, Karoly ; Groot, Kate ; Hebert, Francine ; Arencibia, Jose M. / Inhibition of growth of ES-2 human ovarian cancers by bombesin antagonist RC-3095, and luteinizing hormone-releasing hormone antagonist Cetrorelix. In: Cancer Letters. 2001 ; Vol. 171, No. 1. pp. 37-45.
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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 μg/day and Cetrorelix (100 μg/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.",
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