biostudies-otherUnknown90(1)Bajo AMBritish Journal of Cancer245-52https://www.ebi.ac.uk/biostudies/studies/S-EPMC2395331The 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.biostudies-otherEurope PMCBajo AMSchally AVGroot KSzepeshazi KfalseBombesin antagonists inhibit proangiogenic factors in human experimental breast cancers.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.2004-01-01T00:00:00Z2004 Jan2019-08-03T07:10:21Z2019-08-03T07:10:21ZS-EPMC239533110.1038/sj.bjc.6601404