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Antiestrogens
inhibit endothelial cell growth stimulated by angiogenic growth factors
Gagliardi AR, Hennig B, Collins DC
Medical
Research Service, Veterans Affairs Medical Center, Lexington, KY, USA
We have
previously reported that the partial estrogen antagonists, tamoxifen, clomiphene
and nafoxidine, inhibited angiogenesis in vivo in a dose-related manner in the
six-day old chick egg chorioallantoic membrane (CAM) assay.
In the present study, we investigated the effect of basic fibroblast growth
factor (bFGF) and vascular endothelial growth factor (VEGF) on the growth of
porcine pulmonary artery and human dermal microvascular endothelial cells.
Both of these growth factors significantly increased the growth of these cells.
The antiproliferative activity of the partial antiestrogens, tamoxifen,
nafoxidine and clomiphene, and the pure antiestrogen, ICI 182,780, was
determined.
Tamoxifen, clomiphene, nafoxidine and ICI 182,780 significantly inhibited
endothelial cell growth stimulated by bFGF and VEGF.
This inhibition of endothelial cells was not altered by the presence of up to 30
microM of estradiol-17 beta.
These results indicate that the antiangiogenic action of the antiestrogens does
not occur via the estrogen receptor, but by a direct inhibition of growth factor
stimulated endothelial cell growth.
PMID:
8702220 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8702220&dopt=Abstract
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