The Cyclooxygenase-2 Inhibitor, Celecoxib, Prevents the Development of Mammary Tumors in HER-2/neu Mice

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 12; no. 12; pp. 1486 - 1491
• Main Authors: LANZA-JACOBY, Susan, MILLER, Sheldon, FLYNN, John, GALLATIG, Kathleen, DASKALAKIS, Constantine, MASFERRER, Jaime L, ZWEIFEL, Ben S, SEMBHI, Harjeet, RUSSO, Irma H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2003
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Biopsy, Needle; Blotting, Western; Celecoxib; Cyclooxygenase Inhibitors - pharmacology; Disease Models, Animal; Female; General aspects; Genes, erbB-2 - drug effects; Genes, erbB-2 - genetics; Immunohistochemistry; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - prevention & control; Medical sciences; Mice; Mice, Transgenic; Pharmacology. Drug treatments; Pyrazoles; Sensitivity and Specificity; Sulfonamides - pharmacology; Tumors; Prostaglandin-endoperoxide synthase; Enzyme; Cyclooxygenase 2; Treatment efficiency; Rodentia; Enzyme inhibitor; Tumorigenicity; Celecoxib; Malignant tumor; Prevention; Vertebrata; Chemotherapy; Mammalia; Cancerology; Mouse; Animal; C-Onc gene; Tumor; Oxidoreductases; Mammary gland
• ISSN: 1055-9965; 1538-7755

Evidence is now available showing that cyclooxygenase (COX)-2, which is involved in prostaglandin production, is overexpressed in many types of tumors including breast. Several reports have indicated that HER-2/ neu -positive breast tumors are associated with an increased amount of COX-2 protein. In this study, we evaluated the effectiveness of the select COX-1 and COX-2 inhibitors in preventing mammary tumor development in HER-2/ neu transgenic mice. At 4 weeks of age, female HER-2/ neu mice were fed a #5020 rodent diet supplemented with 900 ppm celecoxib, a COX-2 inhibitor, 64 ppm of SC560, a COX-1 inhibitor, or the unsupplemented #5001 diet (control). The incidence of mammary tumors was significantly lower in the celecoxib-fed mice (71%; P = 0.001 versus control) than in the control mice (95%) or in the SC560-fed mice (91%). Celecoxib-treated mice also developed fewer tumors (1.3 ± 1.1 SD; P = 0.039 versus control) than the control mice (2.2 ± 1.2) or the SC560 treated mice (2.3 ± 1.3). The median time to tumor development was 266 days in the control group versus 291 days in the celecoxib-treated group ( P = 0.003 versus control). Lung metastasis was also reduced by treatment with celecoxib. The COX-1 inhibitor SC560 had no protective effect. The protection offered by celecoxib was associated with significantly lower concentrations of prostacyclin and prostaglandin E 2 in mammary tumors and their adjacent mammary glands. Our findings provide additional preclinical evidence to support the clinical studies to investigate the potential effectiveness of COX-2 inhibitors in protecting woman who are at high risk for breast cancer.