Effects of new bombesin antagonists given singly or in combination with a somatostatin analog on nitrosamine-induced pancreatic cancers in hamsters

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

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

In three experiments, hamsters with N-nitroso-bis(2-oxopropyl)amine- induced pancreatic cancers were treated for two months with bombesin/GRP antagonists RC-3095 [D-Tpi6,Leu13'Ψ(CH2NH)Leu14-bombesin(6-14)], RC- 3910-II [D-Tpi6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], RC-3940-II [Hca6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], RC-3950-II [D- Phe6,Leu13'Ψ(CH2N)Tac14-bombesin(6-14)], somatostatin analog RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2), or the combination of RC-3095 with RC-160. All peptides inhibited pancreatic cancers to various degrees, reducing the number of tumorous animals, lowering the weight of tumorous pancreata by 40-55% and decreasing AgNOR numbers which are indicators of cell proliferation rate. Combination therapy with RC-3095 and RC-160 did not inhibit tumors better than single peptides. Among new bombesin/GRP antagonists, RC-3940-II had the strongest inhibitory effect. RC-3950-II and RC-3095 caused similar inhibition, but RC-3910-II was less effective. Tumor inhibitory activity of the bombesin/GRP antagonists was correlated with their binding affinities to bombesin receptors on tumor cells. RC-3940-II caused 50% inhibition of specific binding of [125I-Tyr4]bombesin to tumor cell membranes at 0.96 nM concentration, while the IC50 for RC- 3950-II was 5.27 nM and 12.94 nM for RC-3095. Our findings suggest that in addition to RC-3095, other bombesin/GRP antagonists such as RC-3950-II and especially RC-3940-II could be further developed for therapy of human pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)397-403
Number of pages7
JournalInternational journal of oncology
Volume9
Issue number3
DOIs
StatePublished - Sep 1996
Externally publishedYes

Keywords

  • AgNOR
  • antagonist
  • bombesin
  • bombesin
  • bombesin receptor
  • gastrin-releasing peptide
  • pancreatic cancer
  • somatostatin analog

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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