Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers

Br J Cancer. 2000 May;82(10):1724-31. doi: 10.1054/bjoc.2000.1223.


Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twice daily injections of antagonist MZ-4-71, 10 microg intraperitoneally or 5 microg subcutaneously (s.c.) resulted in a significant 43-45% inhibition of tumour growth. Longer acting GH-RH antagonists, MZ-5-156 and JV-1-36 given once daily at doses of 20 microg s.c. produced a 43-58% decrease in volume and weight of cancers. Histological analyses of HT-29 cancers demonstrated that both a decreased cell proliferation and an increased apoptosis contributed to tumour inhibition. GH-RH antagonists did not change serum IGF-I or IGF-II levels, but significantly decreased IGF-II concentration and reduced mRNA expression for IGF-II in tumours. In vitro studies showed that HT-29 cells produced and secreted IGF-II into the medium, and addition of MZ-5-156 dose-dependently decreased IGF-II production by about 40% as well as proliferation of HT-29 cells. Our studies demonstrate that GH-RH antagonists inhibit growth of HT-29 human colon cancers in vivo and in vitro. The effect of GH-RH antagonists may be mediated through a reduced production and secretion of IGF-II by cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Colonic Neoplasms / chemistry
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Growth Hormone-Releasing Hormone / analogs & derivatives
  • Growth Hormone-Releasing Hormone / antagonists & inhibitors*
  • Growth Hormone-Releasing Hormone / pharmacology
  • HT29 Cells / drug effects
  • HT29 Cells / metabolism
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor II / analysis
  • Insulin-Like Growth Factor II / biosynthesis*
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / biosynthesis*
  • Nucleolus Organizer Region
  • RNA, Messenger / analysis
  • Sermorelin / analogs & derivatives
  • Sermorelin / pharmacology
  • Transplantation, Heterologous


  • JV 1-36
  • MZ 4-71
  • MZ 5-156
  • Neoplasm Proteins
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Sermorelin
  • Growth Hormone-Releasing Hormone