Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

Br J Cancer. 2004 Jan 12;90(1):245-52. doi: 10.1038/sj.bjc.6601404.


The overexpression of angiogenic factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and insulin-like growth factors (IGFs) plays a role in the migration and proliferation of endothelial cells in many cancers. Consequently, we investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonists on the expression of these angiogenic factors, the activities of matrix metalloproteinases (MMPs)-2 and -9, as well as the vascular density in MDA-MB-435 human oestrogen-independent breast cancers. Nude mice bearing orthotopic xenografts of MDA-MB-435 breast cancers were treated with bombesin/GRP antagonists for 6 weeks. Daily administration of 20 microg of RC-3095 or 10 microg of RC-3940-II significantly decreased the weight of MDA-MB-435 cancers by 44 and 53%, respectively. The inhibition of tumour growth was associated with a substantial reduction in the expression of mRNA and protein levels of basic fibroblast growth factor (bFGF), IGF-II and VEGF-A in the tumours. Both bombesin/GRP antagonists significantly decreased the vessel density of the tumours by about 37%, as shown by immunohistochemical detection of vessels on tumour slides. Gelatinolytic activities, detected by zymography, revealed a 33-46% reduction in MMP-9 activity after the treatment with either antagonist. In vitro studies revealed that MDA-MB-435 cells secrete bFGF, IGF-II and VEGF-A, and the secretion of these factors is inhibited by RC-3095 and RC-3940-II. This study demonstrates the antiangiogenic effect of bombesin/GRP antagonists RC-3095 and RC-3940-II, and underscores their possible therapeutic application for treatment of breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Bombesin / analogs & derivatives*
  • Bombesin / antagonists & inhibitors*
  • Bombesin / pharmacology*
  • Breast Neoplasms / physiopathology*
  • Female
  • Fibroblast Growth Factors / biosynthesis
  • Fibroblast Growth Factors / pharmacology
  • Humans
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic*
  • Peptide Fragments / pharmacology*
  • RNA, Messenger / biosynthesis
  • Somatomedins / biosynthesis
  • Somatomedins / pharmacology
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / pharmacology


  • Antineoplastic Agents
  • Peptide Fragments
  • RNA, Messenger
  • Somatomedins
  • Vascular Endothelial Growth Factor A
  • bombesin(6-14), Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-
  • bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-
  • Fibroblast Growth Factors
  • Bombesin