Antagonists of growth hormone-releasing hormone (GH-RH) enhance tumour growth inhibition induced by androgen deprivation in human MDA-Pca-2b prostate cancers

M. Letsch, A. V. Schally, A. Stangelberger, K. Groot, J. L. Varga

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

In the present study, we investigated whether the growth hormone-releasing hormone (GH-RH) antagonist JV-1-38 could enhance the effects of androgen deprivation produced by the anti-androgen Flutamide and luteinising hormone-releasing hormone (LH-RH) agonist Decapeptyl in an experimental model of human androgen-sensitive MDA PCa 2b prostate carcinoma implanted subcutaneously (s.c.) into nude mice. We also evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) the effects of combined treatment on the mRNA expression for prostate-specific antigen (PSA) and measured serum PSA levels. In experiment 1, GH-RH antagonist JV-1-38 greatly inhibited tumour growth in combination with Decapeptyl, but was ineffective when given alone. Thus, combined therapy with JV-1-38 at 20 μg/day and Decapeptyl microcapsules releasing 12.5 μg/day for 29 days inhibited significantly (P<0.01) MDA PCa 2b tumour growth by 65%, compared with controls. Combined treatment also significantly (P<0.05) decreased serum PSA levels by 52% and reduced tumour weight by 54% vs. controls. In experiment 2, GH-RH antagonist JV-1-38 at 20 μg/day likewise showed powerful growth inhibitory effects when combined with Flutamide (25 mg/kg/day) for 21 days. Combined treatment with JV-1-38 and slow-release pellets of Flutamide significantly (P<0.001) inhibited tumour growth by 61% versus controls, and was significantly (P<0.05) more effective than Flutamide or JV-1-38 alone. Combination therapy also reduced significantly (P<0.001) tumour weight and serum PSA levels by 59 and 47%, respectively. The mRNA expression for PSA in MDA PCa 2b tumours was not changed by JV-1-38, Decapeptyl and Flutamide alone or in their respective combinations. Our findings suggest that GH-RH antagonists could enhance the tumour inhibitory effects of androgen deprivation for the primary therapy of patients with advanced prostate carcinoma.

Original languageEnglish (US)
Pages (from-to)436-444
Number of pages9
JournalEuropean Journal of Cancer
Volume40
Issue number3
DOIs
StatePublished - Feb 2004
Externally publishedYes

Keywords

  • Androgen deprivation therapy
  • GH-RH antagonists
  • Prostate cancer
  • Prostate-specific antigen

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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