AIM: To study the effect of nicotine on the migration and invasion of human esophageal squamous carcinoma cells and to investigate whether nimesulide can inhibit the effect of nicotine. METHODS: The esophageal squamous carcinoma cell line (TE-13) was treated with different concentrations of nicotine (100 mu g/mL and 200 mu g/mL) or 200 mu g/mL nicotine plus 100 mu mol/L nimesulide. Cell migration and invasion were measured using migration and invasion chamber systems. COX-2 expression was determined by Western blotting. Matrix metalloproteinase-2 (MMP-2) was analyzed by zymography and ELISA. RESULTS: Nicotine (100 mu g/mL, 200 mu g/mL) enhanced TE-13 cells migration and invasion, and increased the protein expression of COX-2 and the activity of MMP-2. Nicotine (200 mu g/mL) stimulated TE-13 cells migration and invasion which were partly blocked by nimesulide. This was associated with decreased protein expression of COX-2 and decreased activity and protein expression of MMP-2. CONCLUSION: Nicotine enhances the migration and invasion of the esophageal squamous carcinoma cell line, and nimesulide partly blocks the effect of nicotine-enhanced esophageal squamous carcinoma cell migration and invasion. (C) 2009 The WJG Press and Baishideng. All rights reserved.