BACKGROUND: Endothelial cells of human blood vessels (arteries and veins) show high levels of somatostatin subtype-1 receptor (sst(1)). The aim of the present study is to investigate the inhibitory effects of novel somatostatin analogs, highly selective for human sst(1), on in vitro angiogenesis and their modulation of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) expression. MATERIALS AND METHODS: Somatostatin analogs BIM-23745 and BIM-23926 were tested for their ability to prevent proliferation and migration of human endothelial HMEC-1 cells, to modulate VEGF and VEGFR-2 expression and to inhibit sprouting of microvessels from cultured human placental vessel explants in fibrin matrix for 28 days. RESULTS: The somatostatin sst(1 )receptor-selective agonists, BIM-23745 and BIM-23926 showed a suppression of endothelial proliferation (e.g. 10(-6) M BIM-23475, 40.0 +/- 2.1% vs. 100% of controls; 10(-7) M BIM-23926, 55.3 +/- 3.3% vs. 100% of controls), migration (e.g. 10(-7) M BIM-23475, 35.0 +/- 1.56% vs. 100% of controls; 10(-7) M BIM-23926, 53.7 +/- 1.77% vs. 100% of controls) and microvessel sprouting (e.g. 10(-8) M BIM-23475, 42.8 +/- 5.6% vs. 100% of controls; 10(-7) M BIM-23926, 17.2 +/- 11.8% vs. 100% of controls). A small but significant percentage of cells exposed to BIM-23745 and BIM-23926 for 24 h and for 72 h presented typical apoptotic morphology. Moreover, both the analogs significantly inhibit VEGF and VEGFR-2 gene expression in endothelial cells grown for 144 h in a fibrin matrix and the VEGF secretion in conditioned media. CONCLUSIONS: The inhibition of endothelial activities suggests potential therapeutic utility for administration of somatostatin sst(1 )receptor-selective agonists in the proliferative diseases involving angiogenesis.

Background: Endothelial cells of human blood vessels (arteries and veins) show high levels of somatostatin subtype-1 receptor (sst1). The aim of the present study is to investigate the inhibitory effects of novel somatostatin analogs, highly selective for human sst1, on in vitro angiogenesis and their modulation of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) expression. Materials and methods: Somatostatin analogs BIM-23745 and BIM-23926 were tested for their ability to prevent proliferation and migration of human endothelial HMEC-1 cells, to modulate VEGF and VEGFR-2 expression and to inhibit sprouting of microvessels from cultured human placental vessel explants in fibrin matrix for 28 days. Results: The somatostatin sst1receptor-selective agonists, BIM-23745 and BIM-23926 showed a suppression of endothelial proliferation (e.g. 10-6 M BIM-23475, 40·0 ± 2·1% vs. 100% of controls; 10-7 M BIM-23926, 55·3 ± 3·3% vs. 100% of controls), migration (e.g. 10-7 M BIM-23475, 35·0 ± 1·56% vs. 100% of controls; 10 -7 M BIM-23926, 53·7 ± 1·77% vs. 100% of controls) and microvessel sprouting (e.g. 10-8 M BIM-23475, 42·8 ± 5·6% vs. 100% of controls; 10-7 M BIM-23926, 17·2 ± 11·8% vs. 100% of controls). A small but significant percentage of cells exposed to BIM-23745 and BIM-23926 for 24 h and for 72 h presented typical apoptotic morphology. Moreover, both the analogs significantly inhibit VEGF and VEGFR-2 gene expression in endothelial cells grown for 144 h in a fibrin matrix and the VEGF secretion in conditioned media. Conclusions: The inhibition of endothelial activities suggests potential therapeutic utility for administration of somatostatin sst1receptor- selective agonists in the proliferative diseases involving angiogenesis. © 2007 The Authors.

In vitro antiangiogenic activity of selective somatostatin subtype-1 receptor agonists / G. Bocci, M. Culler, A. Fioravanti, P. Orlandi, A. Fasciani, R.L. Colucci, J. Taylor, D. Sadat, R. Danesi, M. DEL TACCA. - In: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0014-2972. - 37:9(2007), pp. 700-708. [10.1111/j.1365-2362.2007.01848.x]

In vitro antiangiogenic activity of selective somatostatin subtype-1 receptor agonists

R. Danesi;
2007

Abstract

Background: Endothelial cells of human blood vessels (arteries and veins) show high levels of somatostatin subtype-1 receptor (sst1). The aim of the present study is to investigate the inhibitory effects of novel somatostatin analogs, highly selective for human sst1, on in vitro angiogenesis and their modulation of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) expression. Materials and methods: Somatostatin analogs BIM-23745 and BIM-23926 were tested for their ability to prevent proliferation and migration of human endothelial HMEC-1 cells, to modulate VEGF and VEGFR-2 expression and to inhibit sprouting of microvessels from cultured human placental vessel explants in fibrin matrix for 28 days. Results: The somatostatin sst1receptor-selective agonists, BIM-23745 and BIM-23926 showed a suppression of endothelial proliferation (e.g. 10-6 M BIM-23475, 40·0 ± 2·1% vs. 100% of controls; 10-7 M BIM-23926, 55·3 ± 3·3% vs. 100% of controls), migration (e.g. 10-7 M BIM-23475, 35·0 ± 1·56% vs. 100% of controls; 10 -7 M BIM-23926, 53·7 ± 1·77% vs. 100% of controls) and microvessel sprouting (e.g. 10-8 M BIM-23475, 42·8 ± 5·6% vs. 100% of controls; 10-7 M BIM-23926, 17·2 ± 11·8% vs. 100% of controls). A small but significant percentage of cells exposed to BIM-23745 and BIM-23926 for 24 h and for 72 h presented typical apoptotic morphology. Moreover, both the analogs significantly inhibit VEGF and VEGFR-2 gene expression in endothelial cells grown for 144 h in a fibrin matrix and the VEGF secretion in conditioned media. Conclusions: The inhibition of endothelial activities suggests potential therapeutic utility for administration of somatostatin sst1receptor- selective agonists in the proliferative diseases involving angiogenesis. © 2007 The Authors.
BACKGROUND: Endothelial cells of human blood vessels (arteries and veins) show high levels of somatostatin subtype-1 receptor (sst(1)). The aim of the present study is to investigate the inhibitory effects of novel somatostatin analogs, highly selective for human sst(1), on in vitro angiogenesis and their modulation of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) expression. MATERIALS AND METHODS: Somatostatin analogs BIM-23745 and BIM-23926 were tested for their ability to prevent proliferation and migration of human endothelial HMEC-1 cells, to modulate VEGF and VEGFR-2 expression and to inhibit sprouting of microvessels from cultured human placental vessel explants in fibrin matrix for 28 days. RESULTS: The somatostatin sst(1 )receptor-selective agonists, BIM-23745 and BIM-23926 showed a suppression of endothelial proliferation (e.g. 10(-6) M BIM-23475, 40.0 +/- 2.1% vs. 100% of controls; 10(-7) M BIM-23926, 55.3 +/- 3.3% vs. 100% of controls), migration (e.g. 10(-7) M BIM-23475, 35.0 +/- 1.56% vs. 100% of controls; 10(-7) M BIM-23926, 53.7 +/- 1.77% vs. 100% of controls) and microvessel sprouting (e.g. 10(-8) M BIM-23475, 42.8 +/- 5.6% vs. 100% of controls; 10(-7) M BIM-23926, 17.2 +/- 11.8% vs. 100% of controls). A small but significant percentage of cells exposed to BIM-23745 and BIM-23926 for 24 h and for 72 h presented typical apoptotic morphology. Moreover, both the analogs significantly inhibit VEGF and VEGFR-2 gene expression in endothelial cells grown for 144 h in a fibrin matrix and the VEGF secretion in conditioned media. CONCLUSIONS: The inhibition of endothelial activities suggests potential therapeutic utility for administration of somatostatin sst(1 )receptor-selective agonists in the proliferative diseases involving angiogenesis.
Human angiogenesis; Somatostatin analogs; Somatostatin subtype-1 receptor
2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1120148
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