LAUSR

The antibiotic salinomycin was recently identified as an antitumor drug for the treatment of several types of solid tumors. However, the effects of salinomycin on the migratory and invasive properties of non-small cell lung cancer (NSCLC) are unclear. This study was aimed to investigate the inhibitory effect and accompanying mechanisms of salinomycin on epithelial-to-mesenchymal transition (EMT) and cell migration induced by transforming growth factor-β1 (TGF-β1). In human A549 and H460 NSCLC, salinomycin strongly blocked the enhancement of cell migration by TGF-β1-induced EMT through recovering the loss of E-cadherin and suppressing the induction of mesenchymal markers as well as the upregulation of TGF-β1-mediated AMPK/SIRT signaling activity. We demonstrated that salinomycin was 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, salinomycin could inhibit TGF-β1-enhanced migration and invasion of A549 and H460 cells. MMP-2 and MMP-9 downregulation enhanced the reversal of TGF- β1-induced EMT by salinomycin. In contrast, AMPK/SIRT upregulation promoted TGF- β1-induced EMT. Salinomycin can inhibit TGF-β1-induced EMT and suppress lung cancer cell migration and invasion via downregulation of MMP-2 and MMP-9. Our findings implicate overexpressed AMPK/SIRT1 as a potential therapeutic target to reverse TGF-β1-induced EMT and to prevent lung cancer cell migration and invasion.