Suppression of tumor growth by growth hormone-releasing hormone antagonist JV-1-36 does not involve the inhibition of autocrine production of insulin-like growth factor II in H-69 small cell lung carcinoma

Hippokratis Kiaris, Andrew V. Schally, Jozsef L. Varga

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Although a high antitumor activity of growth hormone releasing hormone (GHRH) antagonists has been demonstrated in various tumors, the mechanism of action of these peptide analogs remains poorly understood. An association has been observed between the antitumor effects of GHRH antagonists and the inhibition of insulin-like growth factors (IGFs), but it is not clear whether the suppression of IGFs is obligatory for the action of GHRH antagonists. In the present study we investigated various components of the IGF system in H-69 small cell lung carcinoma (SCLC) xenografted into nude mice and treated with GHRH antagonist JV-1-36. After 31 days of treatment with JV-1-36, tumor weight was inhibited by about 70% as compared with the controls. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that H-69 tumors express mRNAs for IGF-II and IGF-receptors- (IGFR-) I and II, but not for IGF-I. The levels of mRNA for IGF-II and IGFR-I and -II were not affected by the treatment with JV-1-36. Exposure to antibody IRa, which blocks the binding of IGF-I and -II to IGFR-I, inhibited the proliferation of H-69 cells in vitro, indicating that IGF-II present in the tumors might stimulate the proliferation of H-69 SCLC in an autocrine manner. Collectively our results suggest that inhibition of tumor growth by GHRH antagonists is not associated with the suppression of the autocrine stimulation by IGF-II in H-69 SCLC. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalCancer letters
Volume161
Issue number2
DOIs
StatePublished - Dec 20 2000
Externally publishedYes

Keywords

  • Autocrine growth factor
  • Cancer therapy
  • Growth hormone releasing hormone
  • Insulin-like growth factor receptors
  • Insulin-like growth factors
  • Peptide analogs

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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