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

I. Chatzistamou, Andrew V Schally, B. Sun, P. Armatis, K. Szepeshazi

Research output: Contribution to journalArticle

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Abstract

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% (P < 0.05) and 73.5% (P < 0.05) respectively, after 25 days, compared to controls. RC-3095 at a dose of 20 μg per day reduced the volume of OV-1063 tumours by 47.7% (P = 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 (P < 0.05). RT-PCR analysis showed that OV-1063 tumours expressed mRNA for bombesin receptor subtypes BRS-1, BRS-2, and BRS-3. In OV-1063 cells cultured in vitro, GRP(14-27) induced the expression of mRNA for c-jun 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% (P < 0.05) and 45% (P = 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. (C) 2000 Cancer Research Campaign.

Original languageEnglish
Pages (from-to)906-913
Number of pages8
JournalBritish Journal of Cancer
Volume83
Issue number7
StatePublished - Oct 2 2000
Externally publishedYes

Fingerprint

Bombesin
Oncogenes
Bombesin Receptors
Gastrin-Releasing Peptide
Growth
Carcinoma
Nude Mice
Ovarian Neoplasms
Messenger RNA
Neoplasms
Hormone Antagonists
fos Genes
Tumor Burden
Gonadotropin-Releasing Hormone
Cultured Cells
Intercellular Signaling Peptides and Proteins
Down-Regulation
Ovarian epithelial cancer
Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-bombesin(6-14)
Cell Line

Keywords

  • Bombesin/GRP antagonists
  • C-fos
  • C-jun
  • Cancer therapy
  • LH-RH antagonist
  • Ovarian tumours

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibition of growth of OV-1063 human epithelial ovarian cancers and c-jun and c-fos oncogene expression by bombesin antagonists. / Chatzistamou, I.; Schally, Andrew V; Sun, B.; Armatis, P.; Szepeshazi, K.

In: British Journal of Cancer, Vol. 83, No. 7, 02.10.2000, p. 906-913.

Research output: Contribution to journalArticle

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abstract = "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{\%} (P < 0.05) and 73.5{\%} (P < 0.05) respectively, after 25 days, compared to controls. RC-3095 at a dose of 20 μg per day reduced the volume of OV-1063 tumours by 47.7{\%} (P = 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 (P < 0.05). RT-PCR analysis showed that OV-1063 tumours expressed mRNA for bombesin receptor subtypes BRS-1, BRS-2, and BRS-3. In OV-1063 cells cultured in vitro, GRP(14-27) induced the expression of mRNA for c-jun 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{\%} (P < 0.05) and 45{\%} (P = 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. (C) 2000 Cancer Research Campaign.",
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AU - Schally, Andrew V

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AU - Armatis, P.

AU - Szepeshazi, K.

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