Tranilast Inhibits TGF-β1–induced Epithelial-mesenchymal Transition and Invasion/Metastasis <i>via</i> the Suppression of Smad4 in Human Lung Cancer Cell Lines
Koji Takahashi, Toshi Menju, Shigeto Nishikawa, Ryo Miyata, Satona Tanaka, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Masatsugu Hamaji, Akihiro Ohsumi, Toyofumi F. Chen‐Yoshikawa, Toshihiko Satō, Makoto Sonobe, Hiroshi Date
Abstract
BACKGROUND/AIM: Transforming growth factor β1 (TGF-β1) is an important epithelial-mesenchymal transition (EMT) activator that regulates the expression of E-cadherin and vimentin through Smad signalling. Tranilast is an anti-allergic drug that inhibits TGF-β1, and is used in the treatment of keloids and hypertrophic scars. We investigated whether tranilast inhibits TGF-β1-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-β1/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-β1-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-β1-induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.