The role of activation of the ferroptosis pathway in the inhibition of esophageal cancer proliferation and metastasis by realgar
10.16438/j.0513-4870.2022-0203
- VernacularTitle:铁死亡通路激活在雄黄抑制食管癌增殖和转移中的作用
- Author:
Xue-lian ZHANG
1
;
Ru-yi YANG
2
;
Hong-bin WANG
2
;
Zhao SUN
2
;
Jun WANG
2
;
Qiu-ping WANG
2
;
Fa-zhang CHEN
1
Author Information
1. Medical College of Qinghai University, Xining 810001, China
2. Department of Integrative Medicine, Affiliated Hospital of Qinghai University, Xining 810001, China
- Publication Type:Research Article
- Keywords:
esophageal cancer;
realgar;
ferroptosis;
cell invasion;
cell migration;
cell proliferation
- From:
Acta Pharmaceutica Sinica
2022;57(11):3322-3330
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to investigate the role of activation of the ferroptosis pathway in the inhibition of esophageal cancer proliferation and metastasis by realgar, using esophageal cancer Eca109 and KYSE150 cells as the target cells. The rate of inhibition and half-inhibitory concentration (IC50) were measured by the CCK-8 method; clone formation ability was measured by clone formation assay; the changes in reactive oxygen species (ROS) were detected by flow cytometry; the ultrastructure of the cells was observed by transmission electron microscopy; the distribution of intracellular iron particles was observed by Prussian blue staining; the expression of glutathione peroxidase 4 (GPX4) was detected by immunofluorescence staining; the scratch assay was used to detect the cell migration ability; the Transwell assay was used to detect the cell invasion ability; and western blotting was used to detect E-cadherin, Slug and N-cadherin protein expression in the cells. The results show that realgar inhibited the proliferation of Eca109 and KYSE150 cells in a time- and concentration-dependent manner, and the IC50 of Eca109 and KYSE150 cells was 64.297 and 51.337 μmol‧L-1, respectively. Compared with the control group, many mitochondria in the cytoplasm of Eca109 and KYSE150 cells in the realgar 2IC50 group were swollen and blue-stained particles of different sizes and amounts were found, and ROS fluorescence intensity was significantly increased while GPX4 protein expression was significantly reduced (P < 0.01). Compared with the realgar group, the proliferation, migration, membrane penetration and Slug and N-cadherin protein expression were significantly increased, and the cell inhibition rate and E-cadherin protein expression were significantly decreased in Eca109 and KYSE150 cells in the realgar+ZVAD-FMK group (P < 0.05). The proliferation, migration, membrane penetration and Slug and N-cadherin protein expression were significantly decreased, and the cell inhibition rate and E-cadherin protein expression were significantly increased of Eca109 and KYSE150 cells in the realgar +erastin group (P < 0.05). The above results show that realgar inhibited the proliferation of Eca109 and KYSE150 cells and induced partial ferroptosis in the cells, and the proliferation and metastasis effects of realgar on esophageal cancer cells may work through partial ferroptosis pathway activation.
