Adenocarcinoma, Animals, Apoptosis, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Female, Isoenzymes, Mammary Neoplasms, Experimental, Mice, Mice, Inbred BALB C, Neoplasm Metastasis, Neovascularization, Pathologic, Prostaglandin-Endoperoxide Synthases, Pyrazoles, Sulfonamides
Royal College of Surgeons in Ireland
Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50,000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8+/-0.4 mm, tumours were excised and the mice were randomised into two groups (n=12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50,000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days (n=12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases.
Medicine and Health Sciences | Surgery
Roche-Nagle G, Connolly EM, Eng M, Bouchier-Hayes DJ, Harmey JH. Antimetastatic activity of a cyclooxygenase-2 inhibitor. British Journal of Cancer. 2004 Jul 19;91(2):359-65.
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