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Updated: Aug 13, 2026
Rat Mesentery Angiogenesis Assay
Published on: June 18, 2011
Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models
K L Blackwell1, Z A Haroon, S Shan
1Department of Medical Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Abstract:
Inhibition of tumor angiogenesis is a therapeutic strategy that can inhibit tumor growth and metastases. The aim of this study was to determine whether the estrogen receptor (ER) ligand drug tamoxifen has antiangiogenic effects. We used three different models of angiogenesis, including measurement of microvessel densities in murine tumors, ex vivo aortic ring assays, and corneal pocket assays. ER-negative fibrosarcoma tumors in tamoxifen-treated ovariectomized rats had significantly less vessel formation compared with untreated animals (median microvessel density, 53.6 versus 94.3 counts/per x 200 field; P = 0.002). Rat aortic rings treated with tamoxifen at several different concentrations demonstrated significantly less vascular sprouting than control rings (P = 0.0001). Corneal pocket assays performed in tamoxifen-treated rats compared with control and estrogen-treated rats demonstrated decreased vascular length (0.88 mm versus 1.26 mm versus 1.47 mm; P = 0.022) and vessel area (21% versus 34% versus 47%; P = 0.018). These three animal models all showed significant inhibition of angiogenesis by tamoxifen and suggest a possible contributory mechanism of ER-independent manipulation by tamoxifen in the treatment and prevention of breast cancer. These studies raise the question as to whether or not newer ER ligand drugs might possess even more potent antiangiogenic effects, which in turn could lead to the broadening of the clinical usefulness of these compounds in a number of diseases. More importantly, these studies suggest that the antiangiogenic effects of tamoxifen are due, in part, to ER-independent mechanisms.
Insights
Tamoxifen, a drug targeting estrogen receptors, significantly inhibits tumor angiogenesis, a key process in tumor growth. These findings suggest potential new uses for tamoxifen and similar drugs in cancer treatment and prevention.
Area of Science:
- Oncology
- Pharmacology
- Vascular Biology
Background:
- Tumor angiogenesis, the formation of new blood vessels, is crucial for tumor growth and metastasis.
- Inhibiting angiogenesis is a recognized therapeutic strategy for cancer treatment.
- Tamoxifen is an estrogen receptor (ER) ligand drug primarily used in breast cancer therapy.
Purpose of the Study:
- To investigate the potential antiangiogenic effects of tamoxifen.
- To determine if tamoxifen can inhibit blood vessel formation in various experimental models.
- To explore the mechanisms underlying tamoxifen's antiangiogenic activity, including ER-independent pathways.
Main Methods:
- Utilized three distinct models of angiogenesis: murine tumor microvessel density measurement, ex vivo rat aortic ring assays, and in vivo rat corneal pocket assays.
- Assessed vascularization by quantifying microvessel density, vascular sprouting, and vessel length/area.
- Administered tamoxifen to ovariectomized rats and compared outcomes with control and estrogen-treated groups.
Main Results:
- Tamoxifen significantly reduced microvessel density in ER-negative fibrosarcoma tumors (53.6 vs. 94.3 counts/field, P=0.002).
- Tamoxifen markedly inhibited vascular sprouting in rat aortic ring assays (P=0.0001).
- Corneal pocket assays showed decreased vascular length (0.88 mm vs. 1.26 mm, P=0.022) and vessel area (21% vs. 34%, P=0.018) in tamoxifen-treated rats.
Conclusions:
- Tamoxifen demonstrates significant antiangiogenic effects across multiple experimental models.
- These findings suggest that tamoxifen's antiangiogenic properties may involve estrogen receptor-independent mechanisms.
- The antiangiogenic activity of tamoxifen supports its potential role in breast cancer treatment and prevention, and hints at broader applications for ER ligand drugs.
