南方医科大学学报2025，Vol.45Issue(7)：1363-1371,9.DOI:10.12122/j.issn.1673-4254.2025.07.02
双术汤通过P53/SLC7A11/GPX4通路诱导胃癌细胞铁死亡
Shuangshu Decoction inhibits growth of gastric cancer cell xenografts by promoting cell ferroptosis via the P53/SLC7A11/GPX4 axis
摘要
Abstract
Objective 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.Conclusion SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.关键词
胃癌/网络药理学/生物信息学/分子对接/双术汤/铁死亡/P53/SLC7A11/GPX4通路Key words
gastric cancer/network pharmacology/bioinformatics/molecular docking/Shuangshu Decoction/ferroptosis/P53/SLC7A11/GPX4 pathway引用本文复制引用
陈鑫源,吴成挺,李瑞迪,潘雪芹,张耀丹,陶俊宇,林才志..双术汤通过P53/SLC7A11/GPX4通路诱导胃癌细胞铁死亡[J].南方医科大学学报,2025,45(7):1363-1371,9.基金项目
国家自然科学基金(82060834) （82060834）
广西自然科学基金(2024GXNSFAA010240)Supported by National Natural Science Foundation of China(82060834). （2024GXNSFAA010240）
