title: Celecoxib and sulindac inhibit TGF-β1-induced epithelial-mesenchymal transition and suppress lung cancer migration and invasion via downregulation of sirtuin 1.
abstract: 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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chonbuk National University Medical School, Jeonbuk, Korea.
authors.forename: Byong-Ki
authors.initials: BK
authors.lastname: Cha
authors.affiliation: Departments of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine 344-2 shinyong-dong Iksan, Jeonbuk, Korea.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Departments of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine 344-2 shinyong-dong Iksan, Jeonbuk, Korea.
authors.forename: Ki-Eun
authors.initials: KE
authors.lastname: Hwang
authors.affiliation: Departments of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine 344-2 shinyong-dong Iksan, Jeonbuk, Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Premedicine, School of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Obstetrics & Gynecology, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea.
authors.forename: Byoung-Ryun
authors.initials: BR
authors.lastname: Kim
authors.affiliation: Imaging Science Research Center, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea.
authors.forename: Hong-Young
authors.initials: HY
authors.lastname: Jun
authors.affiliation: Departments of Radiology, Wonkwang University, School of Medicine, Iksan, Jeonbuk, Korea.
authors.forename: Kwon-Ha
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: Departments of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine 344-2 shinyong-dong Iksan, Jeonbuk, Korea.
authors.forename: Eun-Taik
authors.initials: ET
authors.lastname: Jeong
authors.affiliation: Departments of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine 344-2 shinyong-dong Iksan, Jeonbuk, Korea.
authors.forename: Hak-Ryul
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D000068579:Celecoxib / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009361:Neoplasm Invasiveness; D056564:Sirtuin 1 / Q000378:metabolism*; D013467:Sulindac / Q000008:administration & dosage / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D013467:Sulindac; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000068579:Celecoxib
keywords: EMT; SIRT1; celecoxib; lung cancer; sulindac