Chinese Medical Sciences Journal ›› 2020, Vol. 35 ›› Issue (3): 195-206.doi: 10.24920/003670

• Original Article •     Next Articles

Combination of Evodiamine with Berberine Reveals a Regulatory Effect on the Phenotypic Transition of Colon Epithelial Cells Induced by CCD-18Co

Huang Chao1, *(), Xiang Keming2, Liang Bingjun1, Huang Weixuan1, Zhang Fanjun1, Shao Yuwan1, Wang Xiulian2, Liu Haosheng1, Shen Weizeng1   

  1. 1Department of Traditional Chinese Medicine, Affiliated Bao’an Hospital of Shenzhen, Southern Medical University, Shenzhen 518100, China
    2Community Healthy Service Center, Shenzhen Bao’an Traditional Chinese Medicine Hospital Group, Shenzhen 518100, China
  • Received:2019-11-22 Online:2020-09-30 Published:2020-09-25
  • Contact: Huang Chao E-mail:huangchao06@163.com
  • Supported by:
    National Natural Science Foundation of China(81903985, the running period is 2020.1-2022.12);Natural Science Foundation of Guangdong Province(2018A030310060, the running period is 2018.6-2021.5);Postdoctoral Research Foundation of China(2018M643353, the running period is 2018.9-2019.7)
Transdifferentiation exists between stromal cells or between stromal cells and cancer cells. Evodiamine and berberine are predominant pharmacological components of Zuojin pill, a prescription of Traditional Chinese Medicine, playing crucial functions in remolding of tumor microenvironment. In this study, the authors found evodiamine combined with berberine can regulate the differentiation of colon epithelial cells induced by a human colon myofibroblast line CCD-18Co through suppression of activities of TGF-β/Smads signaling.

Abstract:

Objective Transdifferentiation exists between stromal cells or between stromal cells and cancer cells. Evodiamine and berberine are predominant pharmacological components of Zuojin pill, a prescription of Traditional Chinese Medicine, playing crucial functions in remolding of tumor microenvironment. This study aimed to explore the effect of combination of evodiamine with berberine (cBerEvo) on the phenotypic transition of colon epithelial cells induced by tumor-associated fibroblasts, as well as the involved mechanisms.
Methods Human normal colon epithelial cell line HCoEpiC cells were treated with the prepared conditioned medium of CCD-18Co, a human colon myofibroblast line, to induce epithelial-mesenchymal transition. Phase contrast microscope was used to observe the morphological changes. Epithelial-mesenchymal transition markers including E-cadherin, vimentin and alpha-smooth muscle actin (α-SMA) were observed with immunofluorescence microscopy. Migration was assessed by wound healing assay. Western blotting was used to detect the expressions of E-cadherin, vimentin, α-SMA, Snail, ZEB1 and Smads.
Results In contrast to the control, the tumor-associated fibroblasts-like CCD-18Co cells induced down-regulation of E-cadherin and up-regulation of vimentin, α-SMA, Snail and ZEB1 (P<0.05), and promoted migration of HCoEpiCs (P<0.05), with over expression of Smads including Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 (P<0.05), which were abolished by a transforming growth factor-β (TGF-β) receptor inhibitor LY364947 and by cBerEvo in a concentration dependent manner. In addition, cBerEvo-inhibited ratios of p-Smad2/Smad2 and p-Smad3/Smad3 were also dose dependent.
Conclusion The above results suggest that cBerEvo can regulate the differentiation of colon epithelial cells induced by CCD-18Co through suppressing activity of TGF-β/Smads signaling pathway.

Key words: evodiamine, berberine, tumor microenvironment, epithelial-mesenchymal transition, TGF-β signaling

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