A mediator of phosphorylated Smad2/3, evodiamine, in the reversion of TAF-induced EMT in normal colonic epithelial cells

摘要: Purpose Transdifferentiation exists within stromal cells in the tumour microenvironment. Transforming growth factor-β (TGF-β) secreted by tumour-associated fibroblasts (TAFs) affects differentiation states of epithelial cells, including epithelial-mesenchymal transition (EMT). Evodiamine, a natural drug, can regulate differentiation. However, specific effects and relative mechanisms evodiamine remain unknown. Design We used four models to observe influence TAF-like CCD-18Co on colon cell line HCoEpiC: 3D- 2D-mono-culture system, Transwell direct co-culture model. Additionally, we established conditioned medium from cells. The TGF-β pathway inhibitor LY364947 were added. Morphological changes classical EMT markers observed detected using phase contrast microscopy immunofluorescence. Cell migration was measured wound-healing assay. Western blotting performed detect TGF-β/Smad signalling pathway. Results induced EMT-like 2D- 3D-cultured HCoEpiC, accompanied high expression ZEB1 Snail enhancement migration. Moreover, CCD-18Co-derived caused dysfunction EMT. Evodiamine inhibited these HCoEpiC their down-regulated ZEB1/Snail up-regulated phosphorylated Smad2/3 (pSmad2/3). also increased ratios pSmad2/Smad2 pSmad3/Smad3. Conclusion Based our observations, reverse TAF-induced phenotype which may be associated with its mediation Smad2 Smad3 expression.