Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer

• Published in: British journal of cancer 2002-07, Vol.87 (2), p.231-237
• Main Authors: Connolly, E M, Harmey, J H, O'Grady, T, Foley, D, Roche-Nagle, G, Kay, E, Bouchier-Hayes, D J
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - blood supply; Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Adenocarcinoma - pathology; Adenocarcinoma - prevention & control; Adenocarcinoma - secondary; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antineoplastic agents; Apoptosis - drug effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chemotherapy; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; Drug Resistance; Drug Screening Assays, Antitumor; Endothelial Growth Factors - biosynthesis; Epidemiology; Experimental Therapeutics; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Indomethacin - pharmacology; Indomethacin - therapeutic use; Isoenzymes - antagonists & inhibitors; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Lymphokines - biosynthesis; Mammary Neoplasms, Experimental - blood supply; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - enzymology; Mammary Neoplasms, Experimental - pathology; Medical sciences; Membrane Proteins; Mice; Mice, Inbred BALB C; Molecular Medicine; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - biosynthesis; Neoplasm Transplantation; Neovascularization, Pathologic - drug therapy; Oncology; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Random Allocation; Substrate Specificity; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; Tumor Cells, Cultured - enzymology; Tumor Cells, Cultured - transplantation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600462

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.