Tranilast Inhibits TGF-beta 1-induced Epithelial-mesenchymal Transition and Invasion/Metastasis via the Suppression of Smad4 in Human Lung Cancer Cell Lines

摘要

Background/Aim: Transforming growth factor beta 1 (TGF-beta 1) is an important epithelial-mesenchymal transition (EMT) activator that regulates the expression of E-cadherin and vimentin through Smad signalling. Tranilast is an antiallergic drug that inhibits TGF-beta 1, and is used in the treatment of keloids and hypertrophic scars. We investigated whether tranilast inhibits TGF-beta 1-induced EMT and invasiveness in human non-small cell lung cancer cell lines. Materials and Methods: We examined the effects of tranilast treatment on EMT markers, TGF-beta 1/Smad signalling, and cell invasiveness in A549 and PC14 cells. Tumours from a mouse orthotopic lung cancer model with or without tranilast treatment were also immunohistochemically evaluated. Results: Tranilast increased E-cadherin expression via Smad4 suppression and inhibited cell invasion in TGF-beta 1-stimulated cells. Tranilast treatment of the in vivo mouse model reduced the pleural dissemination of cancer cells and suppressed vimentin and Smad4 expression. Conclusion: Tranilast inhibited TGF-beta 1-induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.