Shuangshu Decoction inhibits growth of gastric cancer cell xenografts by promoting cell ferroptosis via the P53/SLC7A11/GPX4 axis.
10.12122/j.issn.1673-4254.2025.07.02
- Author:
Xinyuan CHEN
1
;
Chengting WU
1
;
Ruidi LI
2
;
Xueqin PAN
3
;
Yaodan ZHANG
3
;
Junyu TAO
1
;
Caizhi LIN
1
Author Information
1. Guangxi University of Chinese Medicine, Nanning 530299, China.
2. Department of Spleen and Gastroenterology, Xianhu Campus of First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530200, China.
3. Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning 530299, China.
- Publication Type:Journal Article
- Keywords:
P53/SLC7A11/GPX4 pathway;
Shuangshu Decoction;
bioinformatics;
ferroptosis;
gastric cancer;
molecular docking;
network pharmacology
- MeSH:
Ferroptosis/drug effects*;
Animals;
Stomach Neoplasms/metabolism*;
Tumor Suppressor Protein p53/metabolism*;
Mice, Nude;
Phospholipid Hydroperoxide Glutathione Peroxidase;
Drugs, Chinese Herbal/pharmacology*;
Humans;
Amino Acid Transport System y+/metabolism*;
Mice;
Cell Line, Tumor;
Cell Proliferation/drug effects*;
Xenograft Model Antitumor Assays
- From:
Journal of Southern Medical University
2025;45(7):1363-1371
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the mechanism of Shuangshu Decoction (SSD) for inhibiting growth of gastric cancer xenografts in nude mice.
METHODS:Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis, and bioinformatics analysis and molecular docking were used to validate the core targets. In the cell experiment, AGS cells were treated with SSD-medicated serum, Fer-1 (a ferroptosis inhibitor), or both, and the changes in cell viability, ferroptosis markers (ROS, Fe2+ and GSH), expressions of P53, SLC7A11 and GPX4, and mitochondrial morphology were examined. In a nude mouse model bearing gastric cancer xenografts, the effects of gavage with SSD, intraperitoneal injection of Fer-1, or their combination on tumor volume/weight, histopathology, and expressions of P53, SLC7A11 and GPX4 levels were evaluated.
RESULTS:The active components in SSD (quercetin and wogonin) showed strong binding affinities to P53. In AGS cells, SSD treatment dose-dependently inhibited cell proliferation, increased ROS and Fe2+ levels, upregulated P53 expression, and downregulated the expressions of SLC7A11 and GPX4, but these effects were effectively attenuated by Fer-1 treatment. SSD also induced mitochondrial shrinkage and increased the membrane density, which were alleviated by Fer-1. In the tumor-bearing mouse models, gavage with SSD significantly reduced tumor size and weight, caused tumor cell necrosis, upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue, and these effects were obviously mitigated by Fer-1 treatment.
CONCLUSIONS:SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.
