广西医科大学学报2024，Vol.41Issue(3)：356-363,8.DOI:10.16190/j.cnki.45-1211/r.2024.03.006
蒽醌修饰物KA-4s抑制SKOV3/DDP细胞增殖并诱导铁死亡
Anthraquinone derivative KA-4s inhibiting the proliferation and inducing ferroptosis of SKOV3/DDP cells
摘要
Abstract
Objective:To investigate the effect of anthraquinone derivative KA-4s on the proliferation of human cisplatin-resistant ovarian cancer SKOV3/DDP cells in vitroand the mechanism of inducing ferroptosis.Meth-ods:SKOV3/DDP cells were divided into control group and different concentrations(2 μmol/L,5 μmol/L and 7 μmol/L)of anthraquinone derivative KA-4s groups.The effects of KA-4s and cisplatin(DDP)alone on the via-bility of SKOV3/DDP cells were determined by MTT assay,the migration ability of SKOV3/DDP cells was de-tected by scratch test,the mitochondrial morphological changes were detected by mitochondrial green fluorescent probe(Mito-Tracker Green),and the mitochondrial ultrastructure was observed by transmission electron micros-copy.Ferroptosis inducer RSL3 was used as a positive control group,intracellular reactive oxygen species(ROS)levels were detected by DCFA-DA fluorescent probe,the total intracellular ferritin content was detected by colorimetry,and the expression of ferroptosis-related proteins GPX4 and FSP1 was detected by western blot-ting.Results:After treatment with KA-4s and DDP for 48 h,the proliferation of ovarian cancer SKOV3/DDP cells was significantly inhibited,and KA-4s had a stronger inhibitory effect than DDP(P＜0.001),and could in-hibit cell migration.After KA-4s treatment,mitochondria were damaged,mitochondrial structure changed,mem-brane density increased,and ridge decreased or even disappeared.Compared with the blank control group,the in-tracellular ROS levels of the positive RSL3 group and KA-4s group were increased(all P＜0.001),the total iron content in 5 μmol/L KA-4s group was significantly increased(P＜0.001),and the expression of GPX4 and FSP1 proteins in ovarian cancer SKOV3/DDP cells was decreased(P＜0.01),but GPX4 expression in the normal ovari-an IOSE80 cells was unchanged.Conclusion:KA-4s can inhibit the proliferation,migration and induce ferropto-sis of SKOV3/DDP cells.关键词
蒽醌修饰物/SKOV3/DDP细胞/铁死亡/谷胱甘肽过氧化物酶4/活性氧Key words
anthraquinone derivative/SKOV3/DDP cells/ferroptosis/glutathione peroxidase 4/reactive oxygen species分类
医药卫生引用本文复制引用
赵英丹,李欣晓,许淑妹,陈强健,杨盈盈,侯华新,黎丹戎..蒽醌修饰物KA-4s抑制SKOV3/DDP细胞增殖并诱导铁死亡[J].广西医科大学学报,2024,41(3):356-363,8.基金项目
国家自然科学基金资助项目(No.82260714) （No.82260714）
广西自然科学基金资助项目(No.2020GXNSFDA238016) （No.2020GXNSFDA238016）
区域性高发肿瘤早期防治研究教育部重点实验室自主课题项目(No.GKE-ZZ202237) （No.GKE-ZZ202237）
