Effect of Selective Cyclooxygenase 2 Inhibitor in TCDD Pre-exposed Thyroid Papillary Carcinoma Cell Line

ABSTRACT

BACKGROUND: Cyclooxygenase 2 (COX-2) is related to carcinogenesis and progression of cancer. COX-2 has been detected in thyroid cancer. This suggests that COX-2 inhibitor may be useful to control the growth of thyroid cancer cells as well as the progression of thyroid cancer. Tetrachlorodibenzodioxin (TCDD), acting as an inflammatory cytokine, directly induces the expression of COX-2. We examine whether TCDD controls the effect of COX-2 inhibitor on thyroid cancer cells. METHODS: The effects of TCDD and celecoxib on thyroid papillary carcinoma cell line (SNU790) were examined using cell proliferation and fluorescence-activated cell sorting analysis. Western blot analysis was performed to determine the expressed COX-2 levels and the cell cycle-related proteins. The matrix metalloproteinase-2 (MMP-2) expression and gelatinolytic activity were examined using real time-polymerase chain reaction and zymography. RESULTS: TCDD directly induced the growth of SNU790 and the expression of cyclin D1, cyclin A, cyclin E, p21 and COX-2. Celecoxib suppressed the growth of SNU790 and the expression of cyclin D1 and cyclin E. Celecoxib reduced the MMP-2 expression and the gelatinolytic activity, but those effects were decreased in the SNU790 by either pre-treatment with TCDD or co-treatment with TCDD and celecoxib. CONCLUSIONS: Celocoxib effect is directly reduced depending on the exposure to TCDD. TCDD exposure should be considered in the treatment with Celecoxib.