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Adenocarcinoma, Angiogenesis Inhibitors, Animals, Apoptosis, Cyclooxygenase 1, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Drug Screening Assays, Antitumor, Endothelial Growth Factors, Female, Gene Expression Regulation, Neoplastic, Humans, Indomethacin, Isoenzymes, Lung Neoplasms, Lymphokines, Mammary Neoplasms, Experimental, Membrane Proteins, Mice, Mice, Inbred BALB C, Neoplasm Proteins, Neoplasm Transplantation, Neovascularization, Pathologic, Prostaglandin-Endoperoxide Synthases, Pyrazoles, Random Allocation, Substrate Specificity, Sulfonamides, Tumor Cells, Cultured, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors


Health Research Board of Ireland


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The effect of selective and non-selective cyclo-oxygenase inhibition on tumour growth and metastasis in an orthotopic model of breast cancer was investigated. 4T1 mammary adenocarcinoma cells were injected into the mammary fat pad of female BALB/c mice. When tumours reached a mean tumour diameter of 8.4+/-0.4 mm, mice were randomised into three groups (n=6 per group) and received daily intraperitoneal injections of the selective cyclo-oxygenase-2 inhibitor, SC-236, the non selective cyclo-oxygenase inhibitor, Indomethacin, or drug vehicle. Tumour diameter was recorded on alternate days. From 8 days after initiation of treatment, tumour diameter in animals treated with either SC-236 or indomethacin was significantly reduced relative to controls. Both primary tumour weight and the number of lung metastases were significantly reduced in the SC-236 and indomethacin treated mice. Microvessel density was reduced and tumor cell apoptosis increased in the primary tumour of mice treated with either the selective or non-selective cyclo-oxygenase inhibitor. In vitro, cyclo-oxygenase inhibition decreased vascular endothelial growth factor production and increased apoptosis of tumour cells. Our results suggest that cyclo-oxygenase inhibitors will be of value in the treatment of both primary and metastatic breast cancer.


Medicine and Health Sciences | Surgery


Connolly EM, Harmey JH, O'Grady T, Foley D, Roche-Nagle G, Kay E, Bouchier-Hayes DJ. Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer. British Journal Cancer. 2002;87(2):231-7.

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