Celecoxib and sulindac inhibit TGF-β1-induced epithelial-mesenchymal transition and suppress lung cancer migration and invasion via downregulation of sirtuin 1
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Byong-Ki Cha1,*, Young-Suk Kim2,*, Ki-Eun Hwang2, Kyung-Hwa Cho2, Seon-Hee Oh3, Byoung-Ryun Kim4, Hong-Young Jun5, Kwon-Ha Yoon6, Eun-Taik Jeong2, Hak-Ryul Kim2
1Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Medical School, Jeonbuk, Korea
2Departments of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine 344-2 shinyong-dong Iksan, Jeonbuk, Korea
3Department of Premedicine, School of Medicine, Chosun University, Gwangju, Korea
4Department of Obstetrics & Gynecology, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea
5Imaging Science Research Center, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea
6Departments of Radiology, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea
*These authors have contributed equally to this work
Hak-Ryul Kim, email: [email protected]
Keywords: celecoxib, sulindac, EMT, SIRT1, lung cancer
Received: December 16, 2015 Accepted: July 26, 2016 Published: August 09, 2016
The non-steroidal anti-inflammatory drugs (NSAIDs) celecoxib and sulindac have been reported to suppress lung cancer migration and invasion. The class III deacetylase sirtuin 1 (SIRT1) possesses both pro- and anticarcinogenic properties. However, its role in inhibition of lung cancer cell epithelial-mesenchymal transition (EMT) by NSAIDs is not clearly known. We attempted to investigate the potential use of NSAIDs as inhibitors of TGF-β1-induced EMT in A549 cells, and the underlying mechanisms of suppression of lung cancer migration and invasion by celecoxib and sulindac. We demonstrated that celecoxib and sulindac were effective in preventing TGF-β1-induced EMT, as indicated by upregulation of the epithelial marker, E-cadherin, and downregulation of mesenchymal markers and transcription factors. Moreover, celecoxib and sulindac could inhibit TGF-β1-enhanced migration and invasion of A549 cells. SIRT1 downregulation enhanced the reversal of TGF-β1-induced EMT by celecoxib or sulindac. In contrast, SIRT1 upregulation promoted TGF-β1-induced EMT. Taken together, these results indicate that celecoxib and sulindac can inhibit TGF-β1-induced EMT and suppress lung cancer cell migration and invasion via downregulation of SIRT1. Our findings implicate overexpressed SIRT1 as a potential therapeutic target to reverse TGF-β1-induced EMT and to prevent lung cancer cell migration and invasion.
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