南方医科大学学报2026,Vol.46Issue(3):532-540,9.DOI:10.12122/j.issn.1673-4254.2026.03.07
硒代胱氨酸通过诱导活性氧产生启动氧化应激损伤抑制结肠癌细胞生长
Selenocystine inhibits colon cancer cell growth by promoting reactive oxygen species generation to trigger oxidative damage
摘要
Abstract
Objective To explore the molecular mechanism by which selenocystine(SeC)inhibits colon cancer cell growth in vitro.Methods Colon cancer cells(RKO,HCT-116,and LoVo)were cultured and treated with 5,10,or 20 μmol/L SeC for 24 h and 48 h.MTT assay was used to detect the cell viability,and wound healing assay was used to examine changes in cell migration.Flow cytometry with PI staining was used to analyze cell cycle arrest and apoptosis.Fluorescence probes were employed to monitor reactive oxygen species(ROS)generation,mitochondrial morphology and membrane potential,and the changes in ferroptosis were evaluated by detecting malondialdehyde(MDA),glutathione(GSH)and ferrous ion(Fe2+)levels;Western blotting was used to detect the changes in protein expressions.Results SeC at all the 3 doses significantly inhibited proliferation and migration of colon cancer cells,down-regulated the expression of cell cycle-related proteins CDK2 and CDK4 and activated the apoptotic proteins PARP and caspase-9.Western blotting showed that SeC decreased the expression of ferroptosis proteins FTH1 and xCT and increased the expression of DMT1.The levels of MDA and Fe2+were increased and GSH level was decreased in SeC-treated cells.Fluorescence staining results showed that SeC treatment induced mitochondrial structure damages and promoted cellular ROS production.SeC treatment also increased phosphorylation of oxidative damage proteins and lowered the expression levels of NRF2 and HO-1 proteins.ROS scavenger significantly reversed the up-regulation of DMT1,PARP and p-H2A.X protein induced by SeC in colon cancer cells.Conclusion SeC induces apoptosis and ferroptosis of colon cancer cells by promoting ROS generation and initiating oxidative damage,suggesting the potential of SeC as a potential chemotherapeutic agent for colon cancer.关键词
硒代胱氨酸/结肠癌/活性氧/氧化应激/凋亡/铁死亡Key words
selenocystine/colon cancer/reactive oxygen species/oxidative stress/apoptosis/ferroptosis引用本文复制引用
宋淇乐,苗益恺,冯小桐,王一凡,刘伟,魏琪,于新汝,陈文文,付晓艳..硒代胱氨酸通过诱导活性氧产生启动氧化应激损伤抑制结肠癌细胞生长[J].南方医科大学学报,2026,46(3):532-540,9.基金项目
国家自然科学基金(81701178) (81701178)
山东省医药卫生科技项目(202513011302)Supported by National Natural Science Foundation of China(81701178). (202513011302)