Mechanism of Modified Xiao Xianxiongtang in Inhibiting Invasion and Metastasis by Targeting Microenvironment of MGC-803 Cells
10.13422/j.cnki.syfjx.20221625
- VernacularTitle:基于MGC-803细胞微环境探讨加味小陷胸汤抑制侵袭迁移作用机制
- Author:
Rui DING
1
;
Jinghui WANG
1
;
Liang WANG
1
;
Jian CHEN
1
;
Jinling HUANG
1
Author Information
1. Anhui University of Chinese Medicine， Hefei 230012， China
- Publication Type:Journal Article
- Keywords:
microenvironment;
modified Xiao Xianxiongtang;
MGC-803 cell;
gastric cancer;
invasion and metastasis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(1):18-25
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effects of the water extract of modified Xiao Xianxiongtang on microenvironment of gastric cancer MGC-803 cells， and to explore its possible mechanism in inhibiting the invasion and metastasis and epithelial-mesenchymal transformation （EMT） of MGC-803 cells and regulating Wnt5a/Ca2+/nuclear factor of activated T-cells （NFAT） signaling pathway by regulating microenvironment. MethodThe model of MGC-803 cells was established by transforming growth factor-β1 （TGF-β1）. The MGC-803 cells were divided into blank group， model group， and modified Xiao Xianxiongtang （10， 20， 40 mg·L-1） groups. After transfection of Wnt5a overexpression plasmid， they were divided into pEX-normal control （NC） group， pEX-Wnt5a group， pEX-NC+modified Xiao Xianxiongtang （40 mg·L-1） group and pEX-Wnt5a+modified Xiao Xianxiongtang （40 mg·L-1） group. The invasion ability， migration ability， key factors of microenvironment， epithelial mesenchymal transformation （EMT） gene， Wnt5a， calcineurin （CaN）， NFAT1， phosphorylated （p）-NFAT1 and NFAT1 nuclear protein expression and cell Ca2+ concentration of MGC-803 cells were observed. ResultCompared with the blank group， the microenvironment in the model group was significantly up-regulated（P<0.01）， and compared with the model group， modified Xiao Xianxiongtang （10，20， 40 mg·L-1） could significantly inhibit the microenvironment（P<0.05， P<0.01）. Further experiments showed that compared with the blank group， the number of invasive cells increased， the scratch rate increased， the microenvironmental factors and EMT gene were activated and the Wnt5a/Ca2+/NFAT pathway was activated in the model group after overexpression of Wnt5a. Compared with the model group， modified Xiao Xianxiongtang could inhibit cell distant invasion and reduce healing， inhibit microenvironment， EMT development， and Wnt5a/Ca2+/NFAT signal transduction， reduce NFAT1 nuclear expression and NFAT1-mediated transcriptional activity， thus reduce cell Ca2+ concentration， and reverse the effect of Wnt5a （P<0.05， P<0.01）. ConclusionModified Xiao Xianxiongtang could regulate Wnt5a/Ca2+/NFAT pathway and inhibit the invasion and metastasis of gastric cancer and EMT progression by improving tumor microenvironment.
