This　study　aimed　to　evaluate　the　radiosensitizing　effect　of　a　COX-2　inhibitor,　NS398,　and　its　mechanism　in　radioresistant　esophageal　cancer　Eca109R50Gy　cells.　NS398　enhanced　radiosensitivity　of　Eca109R50Gy　cells,　characterized　by　redistribution　of　cell　cycle,　inhibition　of　DNA-dependent　protein　kinase　catalytic　subunit　expression　and　induction　of　apoptosis.　NS398　also　reduced　phospho-AKT　level,　upregulated　expression　of　Bax　and　both　procaspase-3　and　active　caspase-3,　and　downregulated　Bcl-2　expression.　Finally,　NS398-induced　radiosensitization　was　partly　reversed　by　insulin-like　growth　factor-1,　but　not　by　prostaglandin　E2.　Our　results　suggest　that　NS398　may　enhance　radiosensitivity　of　Eca109R50Gy　cells　through　blocking　AKT　activation　and　inducing　apoptosis.