Effect of bombesin, gastrin‐releasing peptide (GRP)(14–27) and bombesin/GRP receptor antagonist RC‐3095 on growth of nitrosamine‐induced pancreatic cancers in hamsters

Karoly Szepeshazi, Gabor Halmos, Andrew V. Schally, Kate Groot

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Female Syrian golden hamsters with N-nitroso-bis (2-oxopropyl) amine (BOP)-induced pancreatic cancers were treated for 2 months with bombesin/gastrin-releasing peptide (GRP) antagonist D-Tpi6,Leu13Ψ(CH2NH)Leu14 bombesin(6-14) (RC-3095). Bombesin and GRP(14-27) were also administered alone and in combination with the antagonist RC-3095. RC-3095 exerted a dose-dependent inhibitory effect on growth of pancreatic cancers. The number of animals with pancreatic cancers was significantly lower in the group treated with 60 μg/day of RC-3095 and the weight of tumorous pancreata was reduced. Administration of bombesin or GRP alone did not stimulate the growth of pancreatic tumors and, in fact, had a slightly suppressive effect on cancers which was significantly only in Experiment 1. Bombesin and GRP(14-27) given together with RC-3095 did not nullify the inhibitory effect of the antagonist on pancreatic cancer growth. Actually, a greater inhibition of pancreatic tumors was observed after administration of RC-3095 together with bombesin or GRP, than with RC-3095 alone. The mechanism of action of bombesin, GRP, and bombesin antagonists on pancreatic cancers appears to be complex. The inhibitory effect of bombesin antagonists on pancreatic cancer growth was accompanied by a decrease in the binding capacity of EGF receptors in tumor membranes. Administration of bombesin also caused a down-regulation of EGF recptors and the greatest decrease in binding capacity of EGF receptors was observed after treatment with RC-3095 in combination with GRP. Inhibition of pancreatic cancer can thus be tentatively explained by some common pathways in the action of bombesin, GRP and their antagonists, that could be mediated by interference with EGF-receptor mechanisms.

Original languageEnglish (US)
Pages (from-to)282-289
Number of pages8
JournalInternational Journal of Cancer
Volume54
Issue number2
DOIs
StatePublished - May 8 1993
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this