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

Anticancer Drugs. 2001 Oct;12(9):761-8. doi: 10.1097/00001813-200110000-00008.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Female
  • Growth Hormone-Releasing Hormone / analogs & derivatives*
  • Growth Hormone-Releasing Hormone / antagonists & inhibitors*
  • Growth Hormone-Releasing Hormone / metabolism
  • Growth Hormone-Releasing Hormone / 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


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