Antagonists of growth hormone-releasing hormone and somatostatin analog RC-160 inhibit the growth of the OV-1063 human epithelial ovarian cancer cell line xenografted into nude mice

Ioulia Chatzistamou, Andrew V Schally, Jozsef L. Varga, Kate Groot, Patricia Armatis, Rebeca Busto, Gabor Halmos

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Abstract

The effects of antagonists of GHRH and the somatostatin analog RC-160 on the growth of OV-1063 human epitlhelial ovarian cancer cells xenografted into nude mice were investigated. Treatment with 20 μg/day of the GHRH antagonist JV-1-36 or MZ-5-156 and 60 μg/day of the somatostatin analog RC-160 for 25 days decreased tumor volume by 70.9% (P < 0.01), 58.3% (P < 0.05), and 60.6% (P < 0.01), respectively, vs. the control value. The levels of GH in serum were decreased in all of the treated groups, but only RC-160 significantly reduced serum insulin-like growth factor I (IGF-I). The levels of messenger ribonucleic acid (mRNA) for IGF-I and -II and for their receptors in OV-1063 tumors were investigated by multiplex RT-PCR. No expression of mRNA for IGF-I was detected, but treatment with JV-1-136 caused a 51.8% decrease (P < 0.05) in the level of mRNA for IGF-II in tumors. Exposure of OV-1063 cells cultured in vitro to GHRH, IGF-I, or IGF-II significantly (P < 0.05) stimulated cell growth, but 10-5 mol/L JV-1-36 nearly completely inhibited (P < 0.001) OV-1063 cell proliferation. OV-1063 tumors expressed mRNA for GHRH receptors and showed the presence of binding sites for GHRH. Our results indicate that antagonistic analogs of GHRH and the somatostatin analog RC-160 inhibit the growth of epithelial ovarian cancers. The effects of RC-160 seem to be exerted more on the pituitary GH-hepatic IGF-I axis, whereas GHRH antagonists appear to reduce IGF-II production and interfere with the autocrine regulatory pathway. The antitumorigenic action of GHRH antagonists appears to be mediated by GHRH receptors found in OV-1063 tumors.

Original languageEnglish
Pages (from-to)2144-2152
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number5
DOIs
StatePublished - Jun 5 2001
Externally publishedYes

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Growth Hormone-Releasing Hormone
Somatostatin
Insulin-Like Growth Factor I
Nude Mice
Insulin-Like Growth Factor II
Tumors
Cells
Cell Line
RNA
Growth
Neoplasms
Multiplex Polymerase Chain Reaction
Cell proliferation
Cell growth
Tumor Burden
Serum
Ovarian Neoplasms
Cultured Cells
Binding Sites
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Antagonists of growth hormone-releasing hormone and somatostatin analog RC-160 inhibit the growth of the OV-1063 human epithelial ovarian cancer cell line xenografted into nude mice. / Chatzistamou, Ioulia; Schally, Andrew V; Varga, Jozsef L.; Groot, Kate; Armatis, Patricia; Busto, Rebeca; Halmos, Gabor.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 5, 05.06.2001, p. 2144-2152.

Research output: Contribution to journalArticle

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abstract = "The effects of antagonists of GHRH and the somatostatin analog RC-160 on the growth of OV-1063 human epitlhelial ovarian cancer cells xenografted into nude mice were investigated. Treatment with 20 μg/day of the GHRH antagonist JV-1-36 or MZ-5-156 and 60 μg/day of the somatostatin analog RC-160 for 25 days decreased tumor volume by 70.9{\%} (P < 0.01), 58.3{\%} (P < 0.05), and 60.6{\%} (P < 0.01), respectively, vs. the control value. The levels of GH in serum were decreased in all of the treated groups, but only RC-160 significantly reduced serum insulin-like growth factor I (IGF-I). The levels of messenger ribonucleic acid (mRNA) for IGF-I and -II and for their receptors in OV-1063 tumors were investigated by multiplex RT-PCR. No expression of mRNA for IGF-I was detected, but treatment with JV-1-136 caused a 51.8{\%} decrease (P < 0.05) in the level of mRNA for IGF-II in tumors. Exposure of OV-1063 cells cultured in vitro to GHRH, IGF-I, or IGF-II significantly (P < 0.05) stimulated cell growth, but 10-5 mol/L JV-1-36 nearly completely inhibited (P < 0.001) OV-1063 cell proliferation. OV-1063 tumors expressed mRNA for GHRH receptors and showed the presence of binding sites for GHRH. Our results indicate that antagonistic analogs of GHRH and the somatostatin analog RC-160 inhibit the growth of epithelial ovarian cancers. The effects of RC-160 seem to be exerted more on the pituitary GH-hepatic IGF-I axis, whereas GHRH antagonists appear to reduce IGF-II production and interfere with the autocrine regulatory pathway. The antitumorigenic action of GHRH antagonists appears to be mediated by GHRH receptors found in OV-1063 tumors.",
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AU - Varga, Jozsef L.

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AU - Armatis, Patricia

AU - Busto, Rebeca

AU - Halmos, Gabor

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