Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity

Artur Plonowski, Jozsef L. Varga, Andrew V. Schally, Magdalena Krupa, Kate Groot, Gabor Halmos

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Vasoactive intestinal peptide (VIP) stimulates the proliferation and invasiveness of malignant prostatic cells. Receptors for VIP and the closely related growth hormone-releasing hormone (GH-RH) show considerable homology and are found in prostatic and other carcinomas. Among various analogs of GH-RH synthesized, JV-1-52 is a non-selective VIP/GH-RH antagonist, whereas JV-1-53 is a VIP antagonist devoid of GH-RH antagonistic effect. In our study, nude mice bearing PC-3 human androgen-independent prostate carcinomas were treated with JV-1-52 or JV-1-53 (20 μg/day, s.c.) for 28 days. Both antagonists produced a similar reduction in tumor volume (62-67%, p < 0.01) and tumor weight (59-62%; p < 0.05) vs. controls and extended tumor doubling-time from 9.1 to about 16 days (p < 0.05). To investigate the mechanisms involved, in another study we compared the effects of JV-1-53 with those of somatostatin analog RC-160. VIP antagonist JV-1-53 reduced tumor weight by 67% (p < 0.01) and suppressed the expression of mRNA for c-fos and c-jun oncogenes by about 34% (p < 0.05), without affecting serum levels of insulin-like growth factor-I (IGF-I). In conRC-160 (50 μg/day) reduced serum IGF-I by 19% (p < 0.05), but did not significantly decrease tumor weight, mRNA for VIP and high affinity receptors for VIP were detected on PC-3 tumors. Our results suggest that VIP/GH-RH antagonists can inhibit the growth of androgen-independent prostate cancer by abrogating the autocrine/paracrine mitogenic stimuli of VIP. The ability of GH-RH antagonists to block tumoral VIP receptors, in addition to GH-RH receptors, could be potentially beneficial for prostate cancer therapy.

Original languageEnglish (US)
Pages (from-to)624-629
Number of pages6
JournalInternational Journal of Cancer
Volume98
Issue number4
DOIs
StatePublished - Apr 1 2002
Externally publishedYes

Keywords

  • Androgen-independent prostate cancer
  • Antagonist of vasoactive intestinal peptide
  • Growth hormone-releasing hormone

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity'. Together they form a unique fingerprint.

  • Cite this