Chemopreventive effect of celecoxib and expression of cyclooxygenase-1 and cyclooxygenase-2 on chemically-induced rat mammary tumours

• Published in: International journal of experimental pathology Vol. 83; no. 4; pp. 173 - 182
• Main Authors: Jang, Tae Jung, Jung, Ho Guen, Jung, Ki Hoon, O, Min Ku
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-08-2002; Blackwell Science; Blackwell Science Inc
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - adverse effects; Animals; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Blotting, Western; Celecoxib; Chemotherapy; Current Status Review; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - therapeutic use; Female; Gynecology. Andrology. Obstetrics; Immunohistochemistry - methods; Isoenzymes - metabolism; Mammary gland diseases; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - prevention & control; Medical sciences; Membrane Proteins; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; Pyrazoles; rat mammary tumour; Rats; Rats, Sprague-Dawley; Sulfonamides - therapeutic use; Tumors; Prostaglandin-endoperoxide synthase; Carcinoma; Rat; cyclooxygenase-2; cyclooxygenase-1; rat mammary tumour; Prevention; Mammary gland; Mechanism of action; Biochemical analysis; Enzyme; Treatment efficiency; Rodentia; Malignant tumor; Celecoxib; Gene expression; Anthracene derivatives; Non steroidal antiinflammatory agent; Mammary gland diseases; Pathology; Vertebrata; Experimental disease; Mammalia; Treatment; Animal; Chemical protection; Oxidoreductases; Molecular biology
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1046/j.1365-2613.2002.00228.x

We investigated the chemopreventive effect of celecoxib on 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced rat mammary tumours and also the expression and immunolocalization of cyclooxygenase‐1 (COX‐1) and COX‐2 in the various stages of rat mammary carcinogenesis. Rats were divided into normal control group, DMBA‐control group, 500 p.p.m. celecoxib‐treated group, and 1500 p.p.m. celecoxib‐treated group. Both incidence and multiplicity values of tumour for rats treated with celecoxib were less than those in rats of the DMBA‐control group. The level of prostaglandin E2 was higher in tumours of the DMBA‐control and both celecoxib‐treated groups compared to normal mammary glands of each group. In Western blot analysis, all tumours of the DMBA‐control group expressed COX‐1, whereas normal mammary glands showed insignificant expression. COX‐2 expression was observed in 67% of the DMBA‐control group and 20% of both celecoxib‐treated groups and was absent in normal mammary glands. COX‐1 protein was localized in the nuclear membrane and cytoplasm of epithelial tumour cells abutting on glandular lumen, stromal cells, and endothelial cells. COX‐2 protein was detected in the perinuclear cytoplasm of tumour cells bordering on glandular lumen and surrounding stroma, stromal cells, and vascular smooth muscle. In the DMBA‐control group, invasive carcinoma cells showed higher positive immunoreactivity of COX‐2 than carcinomas in situ and atypical tumours. Tumours displayed an increased number of mast‐like cells with COX‐2 expression in comparison to carcinomas in situ. Our results suggest that COX‐1 and COX‐2 expression in tumour cells and stromal cells play an important role in the various stages of DMBA‐induced rat mammary carcinogenesis. In addition, we reconfirm that celecoxib reduces the growth of DMBA‐induced rat mammary tumours.