Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-<italic style="font-style: italic">β</italic><sub>1</sub> of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca<sup>2+</sup>/NFAT Signaling Pathway

Rui DING; Rui-rui GE; En-yu WANG; Xing-hui HONG; Liang WANG; Peng ZHOU; Jing SHAO; Hai-yan FANG; Hui SHI; Jing-hui WANG; Jin-ling HUANG

doi:10.13422/j.cnki.syfjx.20202326

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Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β₁ of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca²⁺/NFAT Signaling Pathway

更新时间：2021-12-03

- Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β₁ of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca²⁺/NFAT Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 4, Pages: 37-46(2021)
- 作者机构：
  
  1.安徽中医药大学，合肥 230012
  2.中药复方安徽省重点实验室，合肥 230012
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20202326
  CLC： R22;R242;R2-031;R285.5
- Received：18 June 2020，
  
  Published Online：17 September 2020，
  
  Published：20 February 2021
- 稿件说明：
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丁芮,葛瑞瑞,王恩宇等.加味小陷胸汤水提物通过Wnt5a/Ca²⁺/NFAT信号通路抑制TGF-β₁介导的人胃癌MGC-803细胞上皮-间质转化及侵袭迁移[J].中国实验方剂学杂志,2021,27(04):37-46.

DING Rui,GE Rui-rui,WANG En-yu,et al.Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β₁ of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca²⁺/NFAT Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(04):37-46.
丁芮,葛瑞瑞,王恩宇等.加味小陷胸汤水提物通过Wnt5a/Ca²⁺/NFAT信号通路抑制TGF-β₁介导的人胃癌MGC-803细胞上皮-间质转化及侵袭迁移[J].中国实验方剂学杂志,2021,27(04):37-46. DOI： 10.13422/j.cnki.syfjx.20202326.

DING Rui,GE Rui-rui,WANG En-yu,et al.Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β₁ of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca²⁺/NFAT Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(04):37-46. DOI： 10.13422/j.cnki.syfjx.20202326.

摘要

目的

观察加味小陷胸汤水提物对转化生长因子-

（transforming growth factor-

，TGF-

）介导的人胃癌MGC-803细胞上皮-间质转化（epithelial-mesenchymal transformation，EMT）及侵袭迁移能力的影响，探讨其调控Wnt5a/Ca

/活化T细胞核因子（nuclear factor of activated T-cells，NFAT）信号通路抑制MGC-803细胞EMT和侵袭转移的作用机制。

方法

用TGF-

（10 μg·L

-1

）诱导人胃癌MGC-803细胞EMT及侵袭转移模型，分别采用Transwell小室实验、划痕愈合实验、蛋白免疫印迹和免疫荧光法检测细胞侵袭迁移能力，EMT标志蛋白表达和Wnt5a/Ca

/NFAT信号通路关键蛋白表达以及细胞内Ca

浓度。

结果

TGF-

能够显著增强MGC-803细胞侵袭迁移能力（

0.01），下调上皮细胞黏附分子（E-cadherin）水平（

0.01），上调间质细胞标志蛋白（N-cadherin），转录因子（Snail）和细胞骨架蛋白（Vimentin）表达（

0.01），并诱导细胞Wnt5a，钙调神经磷酸酶（calcineurin，CaN），活化T细胞核因子1（nuclear factor of activated T-cells1，NFAT1）总蛋白，磷酸化蛋白p-NFAT1和NFAT1核蛋白表达上调及Ca

胞内蓄积（

0.01）；而加味小陷胸汤（10，20，40 mg·L

-1

）均可明显抑制这一现象，且40 mg·L

-1

效果最佳（

0.05，

0.01）；Wnt5a/Ca

/NFAT信号通路特异性抑制剂（

）-（+）-Bay-K-8644与加味小陷胸汤40 mg·L

-1

均可明显抑制MGC-803细胞经TGF-

介导后的侵袭迁移，上调E-cadherin水平，下调N-cadherin，Snail，Vimentin，Wnt5a，CaN，NFAT1蛋白表达及减少Ca

在胞内蓄积（

0.05，

0.01），且（

）-（+）-Bay-K-8644协同加味小陷胸汤40 mg·L

-1

抑制作用效果更强（

0.05，

0.01）。

结论

以上结果提示加味小陷胸汤能通过Wnt5a/Ca

/NFAT信号通路抑制TGF-

介导的EMT，进而降低MGC-803细胞侵袭迁移能力。

Abstract

Objective

This studu aims to investigate the effect of aqueous extract of modified Xiao Xianxiongtang on the epithelial mesenchymal transition（EMT） and the change of its invasion and migration ability of human gastric cancer MGC-803 cells mediated by transforming growth factor-

（TGF-

），and to explore the mechanism of regulating Wnt5a/Ca

/ activated T-cell nuclear factor（NFAT） signaling pathway to inhibit EMT and invasion and metastasis of MGC-803 cells.

Method

TGF-

（10 μg·L

-1

）was used to induce EMT and the invasion and metastasis model of human gastric cancer MGC-803 cells. Transwell chamber experiment， scratchhealing experiment， Western blot and immunofluorescence assay were used to detect cell invasion and migration ability， expression of EMT marker protein and key protein expression of Wnt5a/Ca

/NFAT signaling pathway， and intracellular Ca

concentration.

Result

Compared with the blank group， TGF-

could significantly enhance the invasion and migration ability of MGC-803 cells（

0.01）， down-regulate the level of E-cadherin（

0.01）， up-regulate protein expressions of N-cadherin， Snail and Vimentin（

0.01）， and induce cell Wnt5a， calcineurin （CaN）， total protein of activated T-cell nuclear factor 1（NFAT1）， up-regulation of phosphorylated proteins p-NFAT1 and NFAT1 nucleoprotein and intracellular accumulation of Ca

（

0.01）. Compared with the TGF-

group， modified Xiao Xianxiongtang （10， 20， 40 mg·L

-1

） could significantly inhibit this phenomenon，and 40 mg·L

-1

had the best effect（

0.05，

0.01）.The specific inhibitors of Wnt5a/Ca

/NFAT signaling pathway （

）-（+）-Bay-K-8644 and modified Xiao Xianxiongtang （40 mg·L

-1

） could significantly inhibit theinvasion and migration of MGC-803 cells mediated by TGF-

， up-regulate the level of E-cadherin， and down-regulate expressions of N-cadherin， Snail， Vimentin， Wnt5a， CaN and NFAT1 proteins and reduce the intracellular accumulation of Ca

（

0.05，

0.01）.Moreover，（

）-（+）-Bay-K-8644 combined with modified Xiao Xianxiongtang （40 mg·L

-1

） had stronger inhibitory effect（

0.05，

0.01）.

Conclusion

These results suggest that modified Xiao Xianxiongtang can inhibit the EMT mediated by TGF-

via Wnt5a/Ca

/NFAT signaling pathway，thereby reducing the invasion and migration ability of MGC-803 cells.

关键词

Keywords

references

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Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β1 of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca2+/NFAT Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20202326

摘要

Abstract

关键词

Keywords

references

Extract from Modified Xiao Xianxiongtang Inhibits Epithelial-mesenchymal Transition and Invasion and Migration Mediated by TGF-β₁ of Human Gastric Cancer MGC-803 Cells via Wnt5a/Ca²⁺/NFAT Signaling Pathway