临床与病理杂志2023，Vol.43Issue(12)：2090-2098,9.DOI:10.11817/j.issn.2095-6959.2023.230208
华蟾素通过铁死亡途径抑制上皮性卵巢癌细胞增殖、迁移与侵袭
Cinobufagin inhibits the proliferation,migration and invasion of epithelial ovarian cancer cells through the ferroptosis pathway
摘要
Abstract
Objective:Ferroptosis plays a pivotal role in the progression of various cancers,including ovarian cancer,and represents a promising therapeutic strategy for cancer intervention.Cinobufagin(CINO)has demonstrated antitumor effects in various cancer types,but its effects on epithelial ovarian cancer and its influence on ferroptosis remain unclear.This study aims to elucidate the impact of CINO on the malignant biological behavior of epithelial ovarian cancer and investigate its potential mechanisms related to ferroptosis. Methods:Ovarian cancer cells A2780 and SKOV3 were treated with gradient concentrations of CINO(0,0.1,1.0,10.0 mg/mL).Cell proliferation was detected using the 5-ethynyl-2'-deoxyuridine(EDU)staining,while cell migration and invasion were assessed using the Transwell assay.Intracellular Fe2+ content was evaluated using FerroOrange staining,and the level of 4-hydroxynonenal(4-HNE)was determined by enzyme-linked immunosorbent assay(ELISA).Intracellular reactive oxygen species(ROS)levels were measured using the dihydroethidium(DHE)probe kit.The expression of solute carrier family 7 member 11(SLC7A11)and transferrin receptor 1(TFR1)was analyzed by western blotting.A2780 and SKOV3 cells were pretreated with ferroptosis inhibitor Ferrostatin-1(Fer-1)and the iron chelator deferoxamine mesylate(DFO)and then treated with 10.0 mg/mL CINO to access cell proliferation,migration,and invasion. Results:CINO dose-dependently inhibited proliferation,invasion,and migration of A2780 cells,increased intracellular Fe2+ and 4-HNE levels,reduced the expression of SLC7A11,and upregulated the expression of TFR1(all P<0.05).Fer-1 and DFO partially reversed the inhibitory effects of CINO on cell proliferation,migration,and invasion in ovarian cancer cells(all P<0.05). Conclusion:CNO inhibits the proliferation,migration,and invasion of ovarian cancer cells,potentially through increasing ferroptosis by regulating the SLC7A11/TFR1 signaling pathway.关键词
华蟾素/上皮性卵巢癌/增殖/迁移/侵袭/铁死亡Key words
cinobufagin/epithelial ovarian cancer/proliferation/migration/invasion/ferroptosis引用本文复制引用
孙慧霞,郭哲,许静,王青,段运峥,朱玲新,王启船..华蟾素通过铁死亡途径抑制上皮性卵巢癌细胞增殖、迁移与侵袭[J].临床与病理杂志,2023,43(12):2090-2098,9.基金项目
河南省医学科技攻关联合共建项目(LHGJ20221047,LHGJ20221051).This work was supported by the Henan Medical Science and Technology Joint Construction Project,China(LHGJ20221047,LHGJ20221051). （LHGJ20221047,LHGJ20221051）
