갑상선 유두암 세포주 TPC-1에서 Cyclooxygenase-2 억제제 NS-398의 증식억제효과

Antiproliferative Effect of NS-398, a Cyclooxygenase-2 Inhibitor in TPC-1 Thyroid Cancer Cell Line

Purpose: Cyclooxygenase (COX) enzymes catalyze the rate- limiting step in arachidonate metabolism. COX-1 is expressed constitutively in many cell types. However COX-2 is an inducible enzyme responsible for prostaglandin production at site of inflammation. Recently, there has been increasing evidence that COX-2 involves in development and progression of human tumors. The aim of the present investigation is to evaluate the antiproliferative effect of NS-398, a selective COX-2 inhibitor, and its mechanism in a papillary thyroid cancer cell line, TPC-1. Methods: We used TPC-1 cell line, NS-398 and EGF. COX-2 expression was detected by RT-PCR and western blot. We used MTT assay to evaluate antiproliferative effect of NS- 398. The mechanisms of growth inhibition were evaluated by apoptosis assay and cell cycle analysis using flow cytometry. Results: COX-2 expression was identified by both RT-PCR and western blot in TPC-1 cells and it was upregulated by serum, EGF (10 ng/ml), and NS-398 (50 mM). NS-398 induced a dose-dependent inhibition of cell proliferation but did not increases apoptotic cell population significantly in the TPC-1 cell line. EGF treatment (10 ng/ml) for 72 hours did not seem to change the antiproliferative effect of NS-398. The proportion of G<SUB>0</SUB>/G<SUB>1</SUB> cell cycle was increased by 10% compared with control after 36 hours of treatment with NS-398. Conclusion: TPC-1 cells expressed COX-2 constitutively and its expression was upregulated by serum, EGF, and NS- 398. The selective COX-2 inhibitor, NS-398 inhibited cell proliferation in TPC-1 cell line rather by cell cycle arrest at G<SUB>0</SUB>/G<SUB>1</SUB> phase than by inducing apoptosis. (Korean J Endocrine Surg 2003;3:106-112)