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Inhibition of experimental angiogenesis by the somatostatin analogue octreotide acetate (SMS 201-995)
1Scuola Superiore di Studi Universitari e di Perfezionamento S. Anna, Via Carducci 40, Italy. mbxdanesi@mail.cnuce.cnr.it
Abstract:
The present study investigates the effect of the somatostatin analogue octreotide acetate (SMS 201-995) on experimental angiogenesis in vitro and in vivo. Octreotide reduced the proliferation of human HUV-EC-C endothelial cells (mean, -45.8% versus controls at 10(-9) M; P < 0.05) as well as the density of the vascular network of the chick chorioallantoic membrane (mean, -35.7% versus controls at 50 microgram; P < 0.05). Furthermore, octreotide significantly inhibited chick chorioallantoic membrane neovascularization by the human MCF-10Aint-2 mammary cells secreting the angiogenic protein FGF-3. The proliferation of endothelial and smooth muscle cells from rat aorta explants on fibronectin was reduced by octreotide 10(-8) M (mean, -32.6% versus controls; P < 0.05), and a similar effect was produced on cells sprouting from explants cultured in fibrin (mean, -52.9% versus controls; P < 0.05). Topical administration of octreotide 10 microgram/day for 6 days inhibited rat cornea neovascularization induced by AgNO3/KNO3 (mean, -50.6% versus controls; P < 0.05). Octreotide 40 microgram/day i.p was tested on angiogenesis in rat mesentery obtained by i.p. injections of compound 48/80, a mast cell degranulating agent, or conditioned medium from MCF-10Aint-2 cells and was able to reduce the extent of neovascularization (mean, -45.6 and -64.1%, respectively, versus controls; P < 0.05). These data provide evidence that octreotide is an inhibitor of experimental angiogenesis in vitro and in vivo.
Insights
Octreotide acetate effectively inhibits experimental angiogenesis by reducing endothelial cell proliferation and neovascularization in various in vitro and in vivo models. This somatostatin analogue demonstrates significant anti-angiogenic properties across multiple experimental systems.
Area of Science:
- Biomedical Research
- Pharmacology
- Cell Biology
Background:
- Angiogenesis, the formation of new blood vessels, is crucial for physiological processes but also implicated in pathological conditions like cancer.
- Somatostatin analogues are used clinically for various conditions, but their direct impact on angiogenesis requires further investigation.
Purpose of the Study:
- To investigate the anti-angiogenic effects of octreotide acetate (SMS 201-995) in vitro and in vivo.
- To determine octreotide's impact on endothelial cell proliferation and neovascularization.
Main Methods:
- In vitro studies using human umbilical vein endothelial cells (HUV-EC-C) and rat aortic explants.
- In vivo studies utilizing chick chorioallantoic membrane (CAM) and rat cornea neovascularization models.
- Assessment of neovascularization in rat mesentery following mast cell degranulation or exposure to angiogenic factors.
Main Results:
- Octreotide significantly reduced endothelial cell proliferation in vitro.
- Inhibition of vascular network density and neovascularization was observed in the chick chorioallantoic membrane model.
- Octreotide suppressed neovascularization in rat cornea and mesentery models.
Conclusions:
- Octreotide acetate exhibits significant anti-angiogenic activity in multiple experimental models.
- These findings suggest octreotide acetate as a potential therapeutic agent targeting angiogenesis-dependent diseases.