Berberine reversed the epithelial-mesenchymal transition of normal colonic epithelial cells induced by SW480 cells through regulating the important components in the TGF- pathway
Berberine reversed the epithelial-mesenchymal transition of normal colonic epithelial cells induced by SW480 cells through regulating the important components in the TGF- pathway
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DOI：
10.1002/jcp.27835
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Pang, Zuoliang
中科院分区：
文献类型：
--
作者：
Huang, Chao;Tao, Liang;Pang, Zuoliang
微环境中基质与肿瘤的相互作用在肿瘤的发生和生长中起着至关重要的作用。间质中的细胞转分化是肿瘤形成的先决条件。靶向相互作用可能是一种很有希望的抗癌策略。小檗碱（BBR）已被证实具有抗癌和抗炎作用。利用transwell共培养系统和条件培养基首次发现结肠癌细胞SW480诱导结肠上皮细胞HCoEpiCs发生梭状形态改变，E-cadherin下调，vimentin和α -平滑肌肌动蛋白上调。条件培养基也促进了HCoEpiCs的迁移。这种转变被转化生长因子受体抑制剂LY364947所抑制。BBR（50和100 μ g/ml）逆转了emt样转变，抑制了HCoEpiCs的迁移。进一步的结果表明，TRII、Smad2、p-Smad3的下调和Smad3的过表达参与了sw480诱导的HCoEpiCs表型转变。此外，BBR上调了TRII、Smad2和p-Smad3的表达。综上所述，我们的研究结果表明，BBR通过介导TRII、Smad2和p-Smad3的表达来发挥抗emt和抗迁移作用。
Stroma-tumor interactions within microenvironment play a crucial role in tumor development and growth. Cellular transdifferentiation in the stroma is a prerequisite for tumor formation. Targeting the interactions maybe a promising anticancer strategy. Berberine (BBR) has been confirmed to have anticancer and anti-inflammatory effects. We found for the first time that colon cancer cells SW480 induced spindle-like morphological changes and downregulation of E-cadherin and upregulation of vimentin and alpha-smooth muscle actin in colon epithelial cells HCoEpiCs by using transwell coculture system and conditioned medium from SW480. The conditioned medium also promoted the migration of HCoEpiCs. This transition was inhibited by a transforming growth factor- receptor inhibitor LY364947. BBR (50 and 100 mu g/ml) reversed the EMT-like transition and repressed the migration in HCoEpiCs. Further results demonstrated that downregulation of TRII, Smad2, p-Smad3, and overexpression of Smad3 participated in the SW480-induced phenotypic transition of HCoEpiCs. In addition, BBR upregulated the expressions of TRII, Smad2, and p-Smad3. In conclusion, our findings suggest that BBR exerts the anti-EMT and antimigration effect by mediating the expression of TRII, Smad2, and p-Smad3.