COX-2 and 5-LOX are up-regulated in ESCC. This study aims to determine the efficacy of COX-2 inhibitor, 5-LOX inhibitor and their combination on ESCC. Nimesulide can suppress cell growth and promote apoptosis, accompanied with a decrease of PGE(2) production. AA861 has the similar effect with a down-regulation of LTB(4). In animal experiment, the tumor volumes in drug-treated groups were significantly smaller with the lowest rates of Ki-67 positive cells. In conclusion, either COX-2 inhibitor or 5-LOX inhibitor can suppress ESCC. Dual inhibition of COX-2 and 5-LOX pathway may present a superior anticancer efficacy to either inhibition of COX-2 or 5-LOX alone. (C) 2011 Elsevier Ireland Ltd. All rights reserved.