Inhibition of growth and metastases of MDA-MB-435 human estrogen-independent breast cancers by an antagonist of growth hormone-releasing hormone.

Abstract

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit the growth of various cancers by mechanism(s) that include the suppression of the insulin-like growth factors (IGF)-I and/or -II. In this study, nude mice bearing orthotopic implants of MDA-MB-435 human estrogen-independent breast carcinoma received 39 days of therapy with GH-RH antagonist JV-1-36 (20 microg/day). The treatment significantly inhibited tumor growth by 71.1% (p<0.01) and nullified the metastatic potential of MDA-MB-435 cells. Four of eight control mice (50%) developed metastases in the lymph nodes and one (12.5%) in the lung, but none of the animals receiving JV-1-36 showed metastatic spread. GH-RH antagonist JV-1-36 inhibited the growth of MDA-MB-435 cells in vitro, while IGF-I stimulated it. However, mRNA for IGF-I or -II was not detected in MDA-MB-435 cells, indicating that the suppression of autocrine IGFs may not be involved in the antiproliferative mechanism. Using ligand competition assays with (125)I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-polymerase chain reaction revealed the expression of mRNA for GH-RH receptor splice variant-1 in MDA-MB-435 tumors. Our results suggest that the antitumorigenic action of GH-RH antagonists on MDA-MB-435 breast cancer could be direct and mediated by tumoral GH-RH receptors.

• Authors: I Chatzistamou, A V Schally, J L Varga, K Groot, R Busto, P Armatis, G Halmos
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 12 Issue 9 Pg. 761-8 (Oct 2001) ISSN: 0959-4973 [Print] England
• PMID: 11593058 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• JV 1-36
• RNA, Messenger
• Receptors, Growth Factor
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II
• Growth Hormone-Releasing Hormone

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Division (drug effects)
• Female
• Growth Hormone-Releasing Hormone (analogs & derivatives, antagonists & inhibitors, metabolism, pharmacology)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Insulin-Like Growth Factor II (metabolism)
• Mice
• Mice, Nude
• Neoplasm Metastasis
• RNA, Messenger (analysis)
• Receptors, Growth Factor (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays