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

Abstract

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.