Inhibition of growth of MDA-MB-231 human breast cancer xenografts in nude mice by bombesin/gastrin-releasing peptide (GRP) antagonists RC-3940-II and RC-3095

M. Miyazaki, N. Lamharzi, A. V. Schally, G. Halmos, K. Szepeshazi, K. Groot, Renzhi Cai

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Bombesin or gastrin-releasing peptide (GRP) may act as autocrine growth factors and play a role in the initiation and progression of breast cancer. We investigated the effect of bombesin/GRP antagonists RC-3095 and RC-3940- II on the growth of the MDA-MB-231 oestrogen-independent human breast cancer cell line xenografted into female nude mice. Bombesin/GRP antagonists, RC- 3095 and RC-3940-II, were administered subcutaneously twice daily at a dose of 10 μg for 5 weeks. The growth of MDA-MB-231 tumours was inhibited during the treatment, as shown by a reduction in tumour volume. RC-3940-II and RC- 3095 significantly decreased the final tumour volume by 72.4% and 57.7%, respectively, and greatly reduced tumour weights. RC-3940-II also significantly increased tumour doubling time and appeared to be more effective than RC-3095 in inhibiting the growth of MDA-MB-231 breast cancers. Serum gastrin and insulin-like growth factor-I (IGF-I) levels in animals treated with RC-3095 or RC-3940-II showed no significant changes as compared with controls. There was a significant decrease in the number of binding sites for epidermal growth factor (EGF), as well as bombesin, in tumour cells after chronic treatment with RC-3095 or RC-3940-II, which might be related to inhibition of tumour growth. Reverse transcription polymerase chain reaction, followed by Southern blot analysis, also showed a reduction in the expression of mRNA for EGF receptors in the group treated with RC-3940-II. Our findings suggest that bombesin/GRP antagonists such as RC-3095 or RC-3940-II could be considered for endocrine therapy for oestrogen-independent breast cancers, but further investigations are necessary.

Original languageEnglish (US)
Pages (from-to)710-717
Number of pages8
JournalEuropean Journal of Cancer
Volume34
Issue number5
DOIs
StatePublished - Apr 1 1998
Externally publishedYes

Keywords

  • Bombesin/GRP antagonists
  • Oestrogen-independent breast cancer
  • Tumour inhibition

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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