基于非靶向代谢组学研究三氧化二砷对白血病K562细胞的毒性机制  

Study on the toxic mechanism of arsenic trioxide on K562 cells based on non-targeted metabolomics

作　　者：任富玉 马强[1] 刘治 李晓晶[1] 苏燕[1] REN Fuyu;MA Qiang;LIU Zhi;LI Xiaojing;SU Yan(Department of Biochemistry and Molecular Biology,Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014040,China)

机构地区：[1]内蒙古科技大学包头医学院生物化学与分子生物学教研室,内蒙古包头014040

出　　处：《包头医学院学报》2024年第5期6-11,共6页Journal of Baotou Medical College

基　　金：2021年包头市卫生健康科技计划项目(wsgkkg029);2022年内蒙古自治区高等学校科学研究项目(NJZZ22063);包头医学院科学研究基金项目(BYJJ-BSJJ202002)。

摘　　要：目的:研究三氧化二砷(As_(2)O_(3))对白血病K562细胞代谢的影响。方法:利用CCK-8法检测As_(2)O_(3)对K562细胞活力的影响;采用超高效液相色谱-质谱技术对As_(2)O_(3)孵育后细胞中的代谢物进行鉴定,筛选出差异代谢物,并进行KEGG富集分析。结果:CCK-8结果显示,As_(2)O_(3)可剂量依赖性地降低K562细胞存活率。非靶向代谢组学检测结果表明,As_(2)O_(3)可导致K562细胞内多种代谢物含量发生显著变化。KEGG富集分析表明,差异代谢物主要富集在谷胱甘肽代谢、铁死亡、亚油酸代谢、牛磺酸代谢、癌症中的胆碱代谢、嘌呤代谢等通路。结论:As_(2)O_(3)可显著降低K562细胞存活率,这可能与影响细胞多种代谢稳态,进而导致细胞增殖抑制、诱导细胞凋亡等有关。此外,As_(2)O_(3)是否会诱导K562细胞发生铁死亡值得深入研究。Objective:To study the effect of arsenic trioxide(As_(2)O_(3))on the metabolism of leukemia K562 cells.Methods:Firstly,the effect of As_(2)O_(3) on the viability of K562 cells was detected by CCK-8 assay.Then,the metabolites in the cells after As_(2)O_(3) incubation were identified by ultra-high performance liquid chromatography-mass spectrometry,and the differential metabolites were screened and KEGG enrichment analysis was performed.Results:CCK-8 results showed that As_(2)O_(3) could decrease the survival rate of K562 cells in a dose-dependent manner.The results of non-targeted metabolomics showed that As_(2)O_(3) could lead to significant changes in the content of multiple metabolites in K562 cells.KEGG enrichment analysis showed that the differential metabolites were mainly enriched in glutathione metabolism,ferroptosis,linoleic acid metabolism,taurine metabolism,choline metabolism in cancer,purine metabolism and other pathways.Conclusion:As_(2)O_(3) can significantly decrease the survival rate of K562 cells,which may be related to the influence of various metabolic homeostasis of cells,resulting in the inhibition of cell proliferation and the induction of apoptosis.In addition,whether As_(2)O_(3) can induce ferroptosis in K562 cells is still worthy of further study.

关 键 词：三氧化二砷 K562 非靶向代谢组学 白血病 

分 类 号：R733.7[医药卫生—肿瘤]