Tranilast Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Invasion/Metastasis via the Suppression of Smad4 in Human Lung Cancer Cell Lines.
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.
['Takahashi|Koji|K|', 'Menju|Toshi|T|', 'Nishikawa|Shigeto|S|', 'Miyata|Ryo|R|', 'Tanaka|Satona|S|', 'Yutaka|Yojiro|Y|', 'Yamada|Yoshito|Y|', 'Nakajima|Daisuke|D|', 'Hamaji|Masatsugu|M|', 'Ohsumi|Akihiro|A|', 'Chen-Yoshikawa|Toyofumi Fengshi|TF|', 'Sato|Toshihiko|T|', 'Sonobe|Makoto|M|', 'Date|Hiroshi|H|']
D000818:Animals D000894:Anti-Inflammatory Agents, Non-Steroidal D045744:Cell Line, Tumor D058750:Epithelial-Mesenchymal Transition D006801:Humans D008175:Lung Neoplasms D008297:Male D051379:Mice D008819:Mice, Nude D009361:Neoplasm Invasiveness D009362:Neoplasm Metastasis D051901:Smad4 Protein D053773:Transforming Growth Factor beta1 D062367:ortho-Aminobenzoates
tranilast Smad4 TGF-β1 EMT