Histone deacetylase inhibitor SAHA-induced epithelial–mesenchymal transition by upregulating Slug in lung cancer cells

SAHA, a member of histone deacetylase inhibitors (HDACIs), which emerged as a class of novel antitumor drug, has been used in clinical treatment of cancers. However, clinical experience of SAHA in solid tumors has been disappointing. Nevertheless, the underlying mechanism of this deficiency is not clearly understood. In the present study, we found that SAHA could induce epithelial–mesenchymal transitions (EMT) in lung cancer A549 cells, which was associated with increased migration capability and cellular morphology changes. We showed that SAHA decreased epithelial marker E-cadherin's expression and increased the expression of mesenchymal marker vimentin. SAHA upregulated the protein and mRNA expression of transcription factor Slug in a time-dependent manner and promoted its nuclear translocation. We further demonstrated that SAHA upregulated Slug expression by promoting Slug acetylation but not influencing the phosphorylation of GSK-3β, a main kinase-controlled Slug expression. Finally, silencing of Slug by siRNA reversed EMT marker expressions and cellular morphology change induced by SAHA, suggesting that Slug plays a crucial role in SAHA-mediated EMT in A549 cells. Our research study provided a better understanding of treatment failure of SAHA in patients with solid tumors. Therefore, more attention should be paid to cancer treatment using SAHA and strategies for reversing EMT before using SAHA would be better if the value of SAHA in the treatment of solid tumors, especially lung cancer, is realized. Correspondence to Xue-gang Liu, Department of Thoracic Surgery, Bengbu Medical College, Bengbu 233000, People's Republic of China Tel: +86 552 3086353; e-mail: xgliu99@126.com Received May 17, 2017 Accepted October 7, 2017 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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