Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Anticancer Res. 2020 Jun;40(6):3287-3296. doi: 10.21873/anticanres.14311.
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.
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.
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.
Tranilast inhibited TGF-β1-induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.
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。
我们检查了曲尼司特治疗对 A549 和 PC14 细胞 EMT 标志物、TGF-β1/Smad 信号和细胞侵袭性的影响。还对有或没有曲尼司特治疗的小鼠原位肺癌模型中的肿瘤进行了免疫组织化学评估。
曲尼司特通过抑制 Smad4 表达增加 E-钙黏蛋白表达，并抑制 TGF-β1 刺激细胞的细胞侵袭。体内小鼠模型中的曲尼司特治疗减少了癌细胞的胸膜扩散，并抑制了波形蛋白和 Smad4 的表达。
曲尼司特通过抑制癌细胞中 Smad4 的表达抑制 TGF-β1 诱导的 EMT 和细胞侵袭/转移。
