曲尼司特抑制 TGF-β1 诱导的上皮-间质转化和侵袭/转移对人肺癌细胞系中 Smad4 的抑制作用。

Tranilast Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Invasion/Metastasis the Suppression of Smad4 in Human Lung Cancer Cell Lines.

机构信息

Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

出版信息

Anticancer Res. 2020 Jun;40(6):3287-3296. doi: 10.21873/anticanres.14311.

DOI:10.21873/anticanres.14311

PMID:32487624

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.

摘要

背景/目的：转化生长因子 β1（TGF-β1）是一种重要的上皮-间充质转化（EMT）激活剂，通过 Smad 信号调节 E-钙黏蛋白和波形蛋白的表达。曲尼司特是一种抗过敏药物，可抑制 TGF-β1，用于治疗瘢痕疙瘩和肥厚性瘢痕。我们研究了曲尼司特是否抑制 TGF-β1 诱导的人非小细胞肺癌细胞系 EMT 和侵袭性。