基于质谱的伪靶向代谢组学揭示了 a2 诱导的胃癌细胞中的代谢变异。

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-04-24 DOI:10.1177/14690667241248444

Juan Li, Ying Liu, Piao Zhou, Qiqi Fan, Hong-Min Liu

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引用次数: 0

摘要

胃癌是世界上发病率和死亡率最高的恶性肿瘤之一。济源奥利多宁衍生物化合物 a2 对胃癌细胞具有卓越的抗增殖活性。为了研究胃细胞对作为新型候选药物的 a2 治疗的反应，我们采用了一种伪靶向代谢组学方法，利用液相色谱串联质谱结合多元统计分析，探讨了 a2 诱导的 MGC-803 胃细胞的代谢变异。结果表明，a2治疗可诱导氨基酸酰-tRNA生物合成、丙氨酸、天冬氨酸和谷氨酸代谢、嘧啶代谢、三羧酸循环等水平发生显著的代谢变化，低剂量组和高剂量组约80%的代谢物下调，包括天冬氨酸、色氨酸、7-磷酸色酮糖、琥珀酸、2'-脱氧腺苷、尿苷、胞苷等。这为 GC 的新疗法提供了证据。

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Mass spectrometry-based pseudotargeted metabolomics reveals metabolic variations in a2-induced gastric cancer cell.

Gastric cancer (GC) is one of the most malignant tumors with high morbidity and mortality in the world. Compound a2, a Jiyuan oridonin derivative, exhibited excellent anti-proliferative activity against GC cells. To investigate the gastric cellular response to a2 therapy as a novel drug candidate, we adopted a pseudotargeted metabolomics method to explore metabolic variation in a2-induced MGC-803 gastric cells using liquid chromatography tandem mass spectrometry combined with multivariate statistical analysis. The results showed that a2 treatment induced significant metabolic changes in the levels of aminoacyl-tRNA biosynthesis, alanine, aspartate and glutamate metabolism, pyrimidine metabolism, and tricarboxylic acid cycle, approximately 80% of the metabolites were down-regulated in the low-dose and high-dose groups including aspartate, tryptophan, sedoheptulose 7-phosphate, succinate, 2'-deoxyadenosine, uridine, cytidine, etc. which can provide evidence for a new therapy of GC.

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.