Your browser doesn't support javascript.
loading
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, I; Schally, A V; Varga, J L; Groot, K; Armatis, P; Busto, R; Halmos, G.
Afiliação
  • Chatzistamou I; Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, Section of Experimental Medicine, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
J Clin Endocrinol Metab ; 86(5): 2144-52, 2001 May.
Article em En | MEDLINE | ID: mdl-11344219
The effects of antagonists of GHRH and the somatostatin analog RC-160 on the growth of OV-1063 human epithelial ovarian cancer cells xenografted into nude mice were investigated. Treatment with 20 microg/day of the GHRH antagonist JV-1-36 or MZ-5-156 and 60 microg/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.
Assuntos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Somatostatina / Hormônio Liberador de Hormônio do Crescimento / Sermorelina / Antineoplásicos Limite: Animals / Female / Humans Idioma: En Revista: J Clin Endocrinol Metab Ano de publicação: 2001 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Somatostatina / Hormônio Liberador de Hormônio do Crescimento / Sermorelina / Antineoplásicos Limite: Animals / Female / Humans Idioma: En Revista: J Clin Endocrinol Metab Ano de publicação: 2001 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos