Inhibition of endothelial proliferation by the somatostatin analogue SOM230.
OBJECTIVE
Somatostatin (SST) modulates exocrine and endocrine secretion, proliferation and apoptosis via five G protein-linked receptors (SSTRs 1-5). Long-acting SST analogues such as Octreotide, and the new analogue SOM230, have been developed for the treatment of neuroendocrine tumours. Octreotide has previously been reported to inhibit endothelial proliferation. We wished to determine if SOM230 is a more potent inhibitor of endothelial cell proliferation than Octreotide.


METHODS
We have determined the expression of SSTRs in proliferating human umbilical vein endothelial cells (HUVECs) in vitro, and determined their response to the somatostatin analogues SOM230 and Octreotide, following vascular endothelial growth factor (VEGF) stimulation.


METHODS
Quantitative RT-PCR and western blotting were used to determine the expression of SSTRs 1-5 in proliferating HUVECs. These cells were grown in media containing 200 pg/ml VEGF and treated with 10(-11) to 10(-6) M Octreotide or SOM230. The WST-1 assay was then used to determine the effects of these analogues on HUVEC proliferation.


RESULTS
Using quantitative RT-PCR and western blotting, HUVECs were found to express SSTRs 1, 2 and 5. SSTRs 3 and 4 were not detected. Using the WST-1 assay, SOM230 was found to significantly inhibit proliferation by up to 46.0% +/- 9.4% (10(-6)-10(-7) M; P < 0.05), whereas in parallel studies Octreotide failed to inhibit HUVEC proliferation.


CONCLUSIONS
The pan SST analogue SOM230 inhibits proliferation of HUVECs, which are unaffected by Octreotide. SOM230 may thus represent a suitable candidate drug for antiangiogenic therapy.
Endocrinology Research Group, Division of Academic Medicine, University of Hull Postgraduate Medical Institute, UK. r.l.hayter@hull.ac.uk
Robyn L
RL
Adams
Ian P
IP
Adams
Stephen W
SW
Lindow
Stephen L
SL
Atkin
D015153:Blotting, Western / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015282:Octreotide / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D017481:Receptors, Somatostatin; D042461:Vascular Endothelial Growth Factor A; C101130:somatostatin receptor type 1; D013004:Somatostatin; C094573:somatostatin receptor 5; C517782:pasireotide; C093733:somatostatin receptor 2; D015282:Octreotide