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

K. Szepeshazi, A. V. Schally, K. Groot, P. Armatis, G. Halmos, F. Hebert, B. Szende, J. L. Varga, M. Zarandi

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67 Citations (Scopus)

Abstract

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 μg intraperitoneally or 5 μg 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 μg 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 MT-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 MT-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. (C) 2000 Cancer Research Campaign.

Original languageEnglish
Pages (from-to)1724-1731
Number of pages8
JournalBritish journal of cancer
Volume82
Issue number10
Publication statusPublished - May 10 2000

Keywords

  • AgNOR
  • Apoptosis
  • Colon cancer
  • GH-RH antagonists
  • IGF-I
  • IGF-I receptor
  • IGF-II

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Szepeshazi, K., Schally, A. V., Groot, K., Armatis, P., Halmos, G., Hebert, F., Szende, B., Varga, J. L., & Zarandi, M. (2000). Antagonists of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers. British journal of cancer, 82(10), 1724-1731.