双硫仑协同奥沙利铂诱导胃癌细胞铁死亡  

Disulfiram synergizes with oxaliplatin to induce ferroptosis in gastric cancer cells

作　　者：喻鑫[1] 刘弋[1] 周波[1] 曹先东[1] Yu Xin;Liu Yi;Zhou Bo;Cao Xiandong(Dept of Gastrointestinal Surgery,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院胃肠外科,合肥230022

出　　处：《安徽医科大学学报》2022年第9期1453-1458,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81801952)。

摘　　要：目的探讨双硫仑(DSF)协同奥沙利铂(O_(xa))联合用药对胃癌细胞BGC-823的协同抑制作用。方法CCK-8实验检测细胞活力,CompuSyn软件做Fraction-Effect协同作用曲线评价联用效果;AnnexinV/PI染色流式细胞术检测细胞凋亡率;碘化吡啶(PI)染色流式细胞术检测细胞死亡率;染色流式细胞术检测脂质过氧化自由基(LipROS)水平变化;qRT-PCR检测铁死亡标记物PTGS2、GPX4、SLC7A11的mRNA表达水平变化。结果DSF与O_(xa)单用或联合用药可通过时间和剂量依赖性抑制胃癌细胞BGC-823增殖,两药联用可发挥明显协同作用,诱导BGC-823胃癌细胞凋亡和铁死亡。DSF与O_(xa)联用可诱导LipROS合成增多,导致促铁死亡调控基因PTGS2 mRNA表达水平明显上升,抑铁死亡调控基因GPX4、SLC7A11的mRNA表达水平明显下降。结论DSF与O_(xa)联用可抑制胃癌BGC-823细胞活力,引起BGC-823细胞凋亡和铁死亡。Objective To investigate the synergistic inhibitory effect of disulfiram(DSF)combined with O_(xa)liplatin(O_(xa))on gastric cancer cells BGC-823.Methods Cell viability was assessed with CCK-8 assay.CompuSyn software was used for fitting the Fraction-Effect curve to evaluate the combined effect of the two agents.AnnexinV/PI staining detected apoptosis rate of BGC-823 by flow cytometry.Pyridine iodide(PI)staining detected the rate of dead cells by flow cytometry.BODIPY 581/591 C11 dye(Invitrogen)staining detected lipid peroxidative free radicals(LipROS)level by flow cytometry.qRT-PCR detected the mRNA levels of ferroptosis-related markers PTGS2,GPX4 and SLC7A11.Results DSF and O_(xa)alone or in combination could inhibit the viability of BGC-823 cells in a time-and dose-dependent manner,and the combination of the two drugs could exert a synergistic effect.DSF synergized with O_(xa)to induce apoptosis and ferroptosis in gastric cancer cells.The combination of DSF and O_(xa)could induce significantly increased LipROS level,resulting in a significant increase in the ferroptosis marker PTGS2mRNA level and a significant decrease in the ferroptotic markers GPX4 and SLC7A11 mRNA levels.Conclusion Disulfiram synergizes with O_(xa)liplatin to inhibit the cell viability,induce BGC-823 cell apoptosis and ferroptosis.

关 键 词：胃癌 双硫仑 奥沙利铂 协同作用 铁死亡 

分 类 号：R735.2[医药卫生—肿瘤]