中国癌症防治杂志2024,Vol.16Issue(4):417-423,7.DOI:10.3969/j.issn.1674-5671.2024.04.06
双硫仑联合二价铜离子诱导铜死亡抑制肝癌细胞Hep3B增殖、迁移和侵袭
Effects of disulfiram combined with Cu2+induced cuproptosis on proliferation,migration and invasion of hepatoma Hep3B cells
摘要
Abstract
Objective To investigate the effects of disulfiram(DSF)combined with Cu2+on the proliferation,migration and invasion of hepatoma Hep3B cells and the underlying mechanism.Methods Hepatoma Hep3B cells were cultured in vitro.DSF(30 nmol/L)solution,Cu2+(1 μmol/L)solution and copper chelating agent ammonium tetrathiomolybdate Ⅵ(ATTM)(30 nmol/L)solution were used individually or combinedly for intervention.The cells treated with dimethyl sulfoxide(DMSO)(30 nmol/L)were used as the control group.CCK-8,scratch test and Transwell cell test were used to detect the proliferation,migration and invasion ability of cells.The expression of copper death related proteins dihydrolipoamide S-acetyltransferase(DLAT)and ferredoxin 1(FDX1)were detected by immunofluorescence assay.Results Compared with the control group,the proliferation,migration and invasion ability of Hep3B cells were significantly decreased after DSF or Cu2+or DSF+Cu2+combined intervention(all P<0.05),and the decrease was more significant in DSF+Cu2+combined intervention(all P<0.0001).After addition of DSF combined with Cu2+to ATTM,the inhibitory effects of DSF combined with Cu2+on the proliferation,migration and invasion of Hep3B cells were reversed,and the proliferation,migration and invasion ability cells were enhanced compared with DSF+Cu2+group(all P<0.05).Compared with the control group,the fluorescence intensity of copper death related proteins DLAT and FDX1 showed no significant increase after DSF or Cu2+intervention,but the fluorescence intensity of DLAT protein increased while that of FDX1 protein decreased after DSF+Cu2+combined intervention,and the expression trend of DLAT and FDX1 proteins was reversed after the addition of ATTM.Conclusions DSF combined with Cu2+can inhibit the proliferation,migration and invasion of Hep3B cells,probably through the induction of cuproptosis.关键词
肝癌/Hep3B细胞/双硫仑/铜死亡/增殖/迁移/侵袭Key words
Hepatoma/Hep3B cells/Disulfiram/Cuproptosis/Proliferation/Migration/Invasion分类
医药卫生引用本文复制引用
唐敏,黄娟婵,韦杏雯,罗雪文,赵伟..双硫仑联合二价铜离子诱导铜死亡抑制肝癌细胞Hep3B增殖、迁移和侵袭[J].中国癌症防治杂志,2024,16(4):417-423,7.基金项目
广西重点研发计划项目(桂科AB24010055) (桂科AB24010055)