p97 inhibitor Eer Ⅰ induces apoptosis and ferroptosis of gastric cancer cell line AGS
10.16352/j.issn.1001-6325.2025.11.1401
- VernacularTitle:p97抑制剂Eer Ⅰ诱导胃癌细胞系AGS的凋亡与铁死亡
- Author:
Wenhua LI
1
;
Runlin WANG
;
Qianpeng KANG
;
Mei HUANG
;
Zhengguang GUO
;
Chunlin ZHANG
;
Yongsheng HUANG
Author Information
1. 中国医学科学院基础医学研究所北京协和医学院基础学院,北京 100005
- Keywords:
gastric cancer;
p97 protein;
cell apoptosis;
ferroptosis
- From:
Basic & Clinical Medicine
2025;45(11):1401-1408
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the molecular mechanism of the induction of gastric cancer cell line AGS death by p97 inhibitor eeyarestatin Ⅰ(Eer Ⅰ).Methods AGS cells were treated with Eer Ⅰ.Then liquid chro-matography-mass spectrometry was used to perform proteome analysis for screening differentially expressed proteins and to find underlying signaling pathways.At the same time,the proteins of related pathway were investi-gated by protein immunoblotting.Cell proliferation was detected using the CCK-8 test kit;Cell apoptosis was detec-ted using TUNEL staining test kit;Liperfluo probe was used to detect ferroptosis-related lipid peroxides.Results In Eer Ⅰ treatment group,there were significant changes in proteins(fold change>1.5 and P<0.05),in which 125 proteins were increased and 132 proteins were decreased.The enrichment analysis of these DEPs showed that Eer Ⅰ might significantly affect cell apoptosis and ferroptosis-related signaling pathways.Furthermore,Eer Ⅰcould increase genomic DNA fragmentation related to cell apoptosis,increase of lipid peroxides in the ferroptosis pathway,causes changes in cell death related proteins,and inhibit the proliferation of gastric cancer cells.Conclusions p97 inhibitor Eer Ⅰ can induce cell apoptosis and ferroptosis in AGS cells,thereby inhibiting tumor cell proliferation.