This investigation was intended to study the expression of cyclooxygenase-2 (COX-2) and mapkinase, and apoptosis related gene expression in normal mammary glands of perimenopausal female rats fed oral celecoxib, a selective COX-2 inhibitor and estrogen. The expression of pERK1/2 showed the similar patterns as COX-2 by the oral treatment of celecoxib and estrogen. It was found that celecoxib induced up-regulation of bcl-2 in mammary gland buds. The regulation of bax was decreased in celecoxib supplemented rats. The bcl-2/bax ratio was higher in celecoxib supplemented rats. However, bcl-2/bax ratio was highest in celecoxib group. The up-regulation of COX-2 was observed in celecoxib in mammary gland buds. The similar trend was not displayed with mapkinase expression. Compared to estrogen feeding, bcl-2 expression was upregulated in celecoxib and down-regulating effect was observed with bax expression. The up-regulation of bcl-2 was accompanied by the decreased expression of COX-2. The oral administration of celecoxib caused significant reduction in bcl-2/bax ratio compared to the control indicating that there might be more apoptotic activity in celecoxib treatment. However, estrogen, a known stimulator of cell proliferation also showed the apoptotic potential compared to control or celecoxib. The increased apoptotic potential by celecoxib or estrogen resulted from the different patterns in bcl-2 or bax regulation. The lowering of bcl-2/bax ratio by celecoxib was resulted from the increased expression of bas, while the reduction of bcl-2/bax observed with estrogen was from the decreased bcl-2 and the increased bax. These findings suggest that both bcl-2 and bax are involved in the apoptotic control of celecoxib, and bcl-2 is a significant factor in apoptotic control of estrogen.

Keywords: Celecoxib, COX-2, Molecular markers related to apoptosis, Perimenopausal female rat, Mammary gland buds