Antagonists of growth hormone-releasing hormone inhibit the growth of U- 87MG human glioblastoma in nude mice

Hippokratis Kiaris, Andrew V Schally, Jozsef L. Varga

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Antagonists of growth hormone-releasing hormone(GH-RH)inhibit the growth of various cancers by mechanisms that involve the suppression of the insulin- like growth factor (IGF)-I and/or IGF-II. In view of the importance of the IGF system in glioma tumorigenesis, the effects of GH-RH antagonists MZ-5-156 and JV-1-36 were investigated in nude mice bearing subcutaneous and orthotopic xenografts of U-87MG human glioblastomas. After 4 weeks of therapy with MZ-5-156 or JV-1-36 at the dose of 20/μg/day per animal, the final volume of subcutaneous U-87MG tumors was significantly (P < .01) decreased by 84% and 76%, respectively, as compared with controls. Treatment with GH-RH antagonists also reduced tumor weight and the levels of mRNA for IGF receptor type I (IGFR-I). A reduction in the mRNA levels for IGF-II was found in tumors of mice treated with MZ-5-156. Treatment with MZ-5-156 or JV-1-36 also extended the survival of nude mice implanted orthotopically with U-87MG glioblastomas by 81% (P < .005) and 18%, respectively, as compared with the controls. Exposure in vitro to GH-RH antagonists MZ-5-156 or JV-1-36 at 1 μM concentration for 24 hours decreased the tumorigenicity of U-87MG cells in nude mice by 10% to 30% and extended the latency period for the development of subcutaneous palpable tumors by 31% to 56%, as compared with the controls. Exposure of U-87MG cells to GH-RH antagonists in vitro also resulted in a time-dependent increase in the mRNA levels of IGFR-II or a decrease in the mRNA levels of IGFR-I. mRNA for GH-RH was detected in U-87MG cells and xenografts implying that GH-RH may play a role in the pathogenesis of this tumor. Our results suggest that GH-RH antagonists MZ-5-156 and JV-136 inhibit the growth of U-87MG human glioblastoma by mechanisms that involve the suppression of IGF system. Antagonistic analogs of GH-RH merit further development for the treatment of malignant glioblastoma.

Original languageEnglish
Pages (from-to)242-250
Number of pages9
JournalNeoplasia
Volume2
Issue number3
StatePublished - May 1 2000
Externally publishedYes

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Growth Hormone-Releasing Hormone
Glioblastoma
Nude Mice
Hormone Antagonists
Growth
Messenger RNA
Insulin-Like Growth Factor II
Somatomedins
Neoplasms
Heterografts
IGF Type 1 Receptor
Tumor Burden
Insulin-Like Growth Factor I
Glioma
MZ 5-156
Carcinogenesis
JV 1-36

Keywords

  • Brain tumors
  • Cancer therapy
  • GH-RH
  • IGF
  • IGF receptor

ASJC Scopus subject areas

  • Cancer Research

Cite this

Antagonists of growth hormone-releasing hormone inhibit the growth of U- 87MG human glioblastoma in nude mice. / Kiaris, Hippokratis; Schally, Andrew V; Varga, Jozsef L.

In: Neoplasia, Vol. 2, No. 3, 01.05.2000, p. 242-250.

Research output: Contribution to journalArticle

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abstract = "Antagonists of growth hormone-releasing hormone(GH-RH)inhibit the growth of various cancers by mechanisms that involve the suppression of the insulin- like growth factor (IGF)-I and/or IGF-II. In view of the importance of the IGF system in glioma tumorigenesis, the effects of GH-RH antagonists MZ-5-156 and JV-1-36 were investigated in nude mice bearing subcutaneous and orthotopic xenografts of U-87MG human glioblastomas. After 4 weeks of therapy with MZ-5-156 or JV-1-36 at the dose of 20/μg/day per animal, the final volume of subcutaneous U-87MG tumors was significantly (P < .01) decreased by 84{\%} and 76{\%}, respectively, as compared with controls. Treatment with GH-RH antagonists also reduced tumor weight and the levels of mRNA for IGF receptor type I (IGFR-I). A reduction in the mRNA levels for IGF-II was found in tumors of mice treated with MZ-5-156. Treatment with MZ-5-156 or JV-1-36 also extended the survival of nude mice implanted orthotopically with U-87MG glioblastomas by 81{\%} (P < .005) and 18{\%}, respectively, as compared with the controls. Exposure in vitro to GH-RH antagonists MZ-5-156 or JV-1-36 at 1 μM concentration for 24 hours decreased the tumorigenicity of U-87MG cells in nude mice by 10{\%} to 30{\%} and extended the latency period for the development of subcutaneous palpable tumors by 31{\%} to 56{\%}, as compared with the controls. Exposure of U-87MG cells to GH-RH antagonists in vitro also resulted in a time-dependent increase in the mRNA levels of IGFR-II or a decrease in the mRNA levels of IGFR-I. mRNA for GH-RH was detected in U-87MG cells and xenografts implying that GH-RH may play a role in the pathogenesis of this tumor. Our results suggest that GH-RH antagonists MZ-5-156 and JV-136 inhibit the growth of U-87MG human glioblastoma by mechanisms that involve the suppression of IGF system. Antagonistic analogs of GH-RH merit further development for the treatment of malignant glioblastoma.",
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