伊利司莫诱导子宫内膜癌细胞发生铜死亡的作用机制OA北大核心CSTPCD

Objective To investigate the mechanism of copper ionophore elesclomol induced cuproptosis in endometrial cancer cells.Methods HEC-1-A cells were treated with different concentrations of copper ion carrier elesclomol and copper chloride.Cell proliferation was detected using a cell counting kit(CCK-8)assay.Enzyme-linked immunosorbent assay(ELISA)detected mitochondrial respiratory chain complexesⅠ,Ⅱ,Ⅲ,and IV.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expression.Western blotting and immunohistochemistry were used to detect protein expression.Results Adding elesclomol or copper chloride alone to HEC-1-A cells did not affect cell survival.However,the simultaneous addition of 50 nmol·L-1 elesclomol and 1 μmol·L-1 copper ions caused a significant decrease in cell survival(P＜0.01).Elesclomol-induced HEC-1-A cell death does not involve the apoptosis mechanism.After treatment with 50 nmol·L-1 elesclomol and 1 μmol·L-1 copper ions in HEC-1-A cells,the levels of mitochondrial respiratory chain complexes Ⅰ,Ⅱ,and Ⅲsignificantly increased.After knocking down ferredoxin 1(FDX1),the cuproptosis in HEC-1-A cells was significantly inhibited(P＜0.01).In addition,FDX1 was under-expressed in endometrial cancer tissues.Conclusion Elesclomol may promote cuproptosis in endometrial cancer cells through the FDX1/mitochondrial respiratory pathway.