IC261 inhibits the epithelial-mesenchymal transition induced by TGF-beta in A549 lung cancer cells

Abstract

Despite rapid advances in cancer diagnosis and therapy, lung cancer continues to be the primary cause of cancer-related mortality. Epithelial mesenchymal transition has been implicated in drug resistance and cancer metastasis. IC261 mediates various pathophysiological processes, including inflammation and tumorigenesis. Therefore, we analyzed the involvement of IC261 in epithelial mesenchymal transition. Pretreatment with IC261 significantly inhibited the expression of transforming growth factor (TGF)-beta 1-induced mesenchymal cell markers, including N-cadherin (N-cad), vimentin (Vim), and beta-catenin (beta-cat), at the mRNA and protein levels in A549 lung cancer cells, which was confirmed using immunofluorescence staining. A migration assay revealed that IC261 treatment strongly inhibited TGF-beta 1-induced migration activity at 24 and 48 h. Additionally, IC261 treatment suppressed the activation of the TGF-beta 1 signaling pathway in A549 cells and phosphorylation of Smad2 and Smad3. Our findings demonstrate that IC261, a selective inhibitor of casein kinase 1, inhibits the TGF-beta 1-induced migration of A549 cells by inhibiting Smad2/3 phosphorylation and downregulating the expression of N-cad, Vim, and beta-cat.