首页|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

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

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目的:研究三氧化二砷(As2 O3)对白血病K562 细胞代谢的影响.方法:利用CCK-8 法检测As2 O3 对K562 细胞活力的影响;采用超高效液相色谱-质谱技术对As2 O3 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,As2 O3 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,As2 O3 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:As2 O3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,As2 O3 是否会诱导K562 细胞发生铁死亡值得深入研究.
Study on the toxic mechanism of arsenic trioxide on K562 cells based on non-targeted metabolomics
Objective:To study the effect of arsenic trioxide(As2 O3)on the metabolism of leukemia K562 cells.Methods:Firstly,the effect of As2 O3 on the viability of K562 cells was detected by CCK-8 assay.Then,the metabo-lites in the cells after As2 O3 incubation were identified by ultra-high performance liquid chromatography-mass spec-trometry,and the differential metabolites were screened and KEGG enrichment analysis was performed.Results:CCK-8 results showed that As2 O3 could decrease the survival rate of K562 cells in a dose-dependent manner.The results of non-targeted metabolomics showed that As2 O3 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 me-tabolism,ferroptosis,linoleic acid metabolism,taurine metabolism,choline metabolism in cancer,purine metabolism and other pathways.Conclusion:As2 O3 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 As2 O3 can induce ferroptosis in K562 cells is still worthy of further study.

Arsenic trioxideK562Non-targeted metabolomics

任富玉、马强、刘治、李晓晶、苏燕

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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

三氧化二砷 K562 非靶向代谢组学 白血病

包头市卫生健康科技计划(2021)内蒙古自治区高等学校科研项目(2022)包头医学院科学研究基金

wsgkkg029NJZZ22063BYJJ-BSJJ202002

2024

包头医学院学报
内蒙古科技大学包头医学院

包头医学院学报

影响因子:0.543
ISSN:1006-740X
年,卷(期):2024.40(5)
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