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.

Abstract

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.

• Authors: I Chatzistamou, A V Schally, J L Varga, K Groot, P Armatis, R Busto, G Halmos
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 86 Issue 5 Pg. 2144-52 (May 2001) ISSN: 0021-972X [Print] United States
• PMID: 11344219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• JV 1-36
• MZ 5-156
• RNA, Messenger
• vapreotide
• Somatostatin
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II
• Sermorelin
• Growth Hormone-Releasing Hormone

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Cell Division (drug effects)
• Female
• Growth Hormone-Releasing Hormone (analogs & derivatives, antagonists & inhibitors, pharmacology, therapeutic use)
• Humans
• Insulin-Like Growth Factor I (analysis, genetics)
• Insulin-Like Growth Factor II (analysis, genetics)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Ovarian Neoplasms (drug therapy, pathology)
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Sermorelin (analogs & derivatives, therapeutic use)
• Somatostatin (analogs & derivatives, therapeutic use)
• Transplantation, Heterologous
• Tumor Cells, Cultured