Inhibition of experimental angiogenesis by the somatostatin analogue octreotide acetate (SMS 201-995).
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.
Danesi
R
R
Scuola Superiore di Studi Universitari e di Perfezionamento S. Anna, Via Carducci 40, Italy. mbxdanesi@mail.cnuce.cnr.it
Agen
C
C
Benelli
U
U
Paolo
A D
AD
Nardini
D
D
Bocci
G
G
Basolo
F
F
Campagni
A
A
Tacca
M D
MD
D000818:Animals; D001011:Aorta; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005337:Fibrin / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D008643:Mesentery / Q000098:blood supply / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin; D014407:Tumor Cells, Cultured; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D017077:Culture Media, Conditioned; D005353:Fibronectins; D003189:p-Methoxy-N-methylphenethylamine; D013004:Somatostatin; D005337:Fibrin; D015282:Octreotide