SLC7A11在DADS诱导K562细胞铁死亡中的作用机制研究  

Mechanism of SLC7A11 in DADS-induced ferroptosis of K562 cells

作　　者：王妍 殷小成[1] 马艳敏 阳敏 曹强强[1] Wang Yan;Yin Xiaocheng;Ma Yanmin(Children’s Medical Center,The First Affiliated Hospital of University of South China,Hengyang,Hunan 421000,China)

机构地区：[1]南华大学附属第一医院儿童医学中心,湖南衡阳421000

出　　处：《湘南学院学报（医学版）》2023年第4期7-11,共5页Journal of Xiangnan University（Medical Sciences）

基　　金：湖南省卫生健康委科研课题(202106010168)。

摘　　要：目的观察溶质载体家族7成员11(solute carrier familly 7 member 11,SLC7A11)在二烯丙基二硫(DADS)诱导K562细胞铁死亡中的作用。方法不同浓度DADS分别处理K562细胞24 h、48 h,用CCK-8法检测细胞活力;不同浓度DADS处理K562细胞48 h,用流式细胞术检测活性氧ROS变化情况;不同浓度铁离子螯合剂DFO处理K562细胞24 h后,再以60 mg/L DADS处理48 h,用Western blot检测谷胱甘肽过氧化物酶4(GPX4)蛋白表达;不同浓度DADS处理K562细胞48 h,用Western blot检测SLC7A11蛋白表达;用SLC7A11-si RNA转染K562细胞,采用q PCR及Western blot检测SLC7A11下调及转染后DADS处理下GPX4蛋白表达情况。结果不同浓度的DADS均能显著抑制K562细胞增殖(P<0.05),且随浓度增高细胞活力逐渐下降(24 h,r=-0.9594;48 h,r=-0.9622);40 mg/L、80 mg/L DADS组的细胞内活性氧水平均高于0 mg/L DADS组(P<0.05),与DADS组相比,DFO能拮抗DADS下调K562细胞GPX4蛋白表达(P<0.05);随DADS浓度增加,K562细胞的SLC7A11蛋白表达逐渐下调(r=-0.9543);与NC-DADS组相比,sh1-DADS组GPX4蛋白表达明显下调(P<0.05)。结论DADS能诱导K562细胞铁死亡,其机制可能与抑制SLC7A11表达有关。Objective To observe the effect of SLC7A11 on ferroptosis induced by diallyl disulfide(DADS)in K562 cells.Methods K562 cells were treated with DADS at different concentrations for 24 h and 48 h,respectively,and cell viability was measured by CCK-8 method.K562 cells were treated with DADS at different concentrations for 48 h and the ROS changes were detected by flow cytometry.K562 cells were treated with different concentrations of iron chelating agent DFO for 24 h,and then treated with 60 mg/L DADS for 48 h.The expression of GPX4 protein was detected by Western blot.K562 cells were treated with different concentrations of DADS for 48 h,and SLC7A11 protein expression was detected by Western blot.K562 cells were transfected with SLC7A11-siRNA,and the down-regulation of SLC7A11 and the expression of GPX4 under DADS treatment after transfection were detected by qPCR and Western blot.Results Different concentrations of DADS significantly inhibited the proliferation of K562 cells(P<0.05),and the cell viability gradually decreased with increasing concentration(24 h,r=-0.9594;48 h,r=-0.9622).The levels of intracellular reactive oxygen species in 40 mg/L and 80 mg/L DADS groups were higher than those in 0 mg/L DADS group(P<0.05).Compared with DADS group,DFO antagonized the down-regulation of GPX4 protein expression in K562 cells by DADS(P<0.05).With the increase in the concentration of DADS,the expression of SLC7A11 protein was progressively down-regulated in K562 cells(r=-0.9543).GPX4 protein expression was significantly down-regulated in the sh1-DADS group compared to the NC-DADS group(P<0.05).Conclusion DADS can induce ferroptosis in K562 cells,and the mechanism may be related to the inhibition of SLC7A11 expression.

关 键 词：二烯丙基二硫 铁死亡 白血病 K562细胞 SLC7A11 

分 类 号：R733.7[医药卫生—肿瘤]