Background: Non-steroidal anti-in ammatory drugs (NSAIDs) has been reported to suppress lung cancer invasion and metastasis. However, the mechanism in lung cancer epithelial-mesenchymal transition (EMT) by NSAIDs is not clearly known. The class IIIdeacetylase sirtuin 1 (SIRT1) possesses both pro- and anticarcinogenic properties. In this study, we investigated the role of NSAIDs as an inhibitor of TGF-ß1-induced EMT, and the underlying mechanisms of suppressing lung cancer migration and invasion by celexiband sulindac. Methods: We evaluated the effi cacy of celecoxib and sulindac in TGF-ß1-induced EMT. EMT-related molecular alterations were detected by western blotting. Electric cell-substrate impedance sensing (ECIS) was used to evaluate the migration and invasion of A549 cells. The matrix metalloproteinase (MMP) gelatinolytic activity was determined by gelatin zymography, and protein expression was measured by western blotting. In addition,SIRT1 was knocked down or overexpressed to determine its role in preventing TGFß1- induced EMT by celecoxib or sulindac. Results: Celecoxib was more effective in preventing TGF-ß1-induced EMT, as compared with sulindac treatment, indicating upregulation of the epithelial marker, E-cadherin, anddownregulation of N-cadherin, mesenchymal and transcription factors. Moreover, ECIS assay showed that celecoxib and sulindac could inhibit TGF-ß1-enhanced migration andinvasion of A549 cells. Increment in MMP-9 expression compared to that of MMP-2 following activation of TGF-ß1 was also observed. However, treatment with celecoxib orsulindac inhibited MMP-9 expression. SIRT1 downregulation enhanced reverse of TGFß1- induced EMT by celecoxib or sulindac. In contrast, SIRT1 upregulation had a relevant role in TGF-ß1-induced EMT.Conclusions: Celecoxib and sulindac can inhibit TGF-ß1-induced EMT and suppress lungcancer migration and invasion via down-regulation of SIRT-1. SIRT1 is positive regulator of TGF-ß1-induced EMT and potential therapeutic target to reverse EMT and to prevent lung cancer progression.