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基于定量蛋白质组学、靶向氨基酸代谢组学、网络药理学及实验验证研究小白菊内酯对肺腺癌氨基酸代谢及氧化应激的影响

Effects of parthenolide on amino acid metabolism and oxidative stress in lung adenocarcinoma based on quantitative proteomic analysis, targeted amino acid metabolomics, network pharmacology, and experimental validation.

作者信息

Liu Jiye, Liu Yu, Li Jiachun, Shen Shuang

机构信息

Department of Rehabilitation Medicine, Teaching Base of Huludao Central Hospital Affiliated to Jinzhou Medical University, Huludao, Liaoning, China.

Department of Family Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Front Oncol. 2025 Sep 1;15:1642866. doi: 10.3389/fonc.2025.1642866. eCollection 2025.

DOI:10.3389/fonc.2025.1642866
PMID:40958860
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12433850/
Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) causes millions of deaths annually worldwide. Parthenolide (PTL), extracted from traditional Chinese herbal medicines, has various biological activities. In this study, we investigated the effects of PTL on amino acid metabolism and oxidative stress in LUAD cells.

METHODS

This study identified differential proteins and potential mechanisms of action of PTL in LUAD cells through label-free quantitative proteomics and protein-protein interaction networks. Combined with targeted amino acid metabolomics, we confirmed the results of GO and KEGG analyses. On this basis, the potential targets of PTL in LUAD were identified through network pharmacology, molecular simulation docking, and molecular dynamics simulations. Finally, the effects of PTL on amino acid metabolism and oxidative stress in LUAD were verified using and experiments.

RESULTS

PTL treatment of LUAD cells resulted in significant changes in expression of 157 proteins. GO and KEGG enrichment analyses showed that these proteins were involved in amino acid metabolism and oxidative stress response. Targeted amino acid metabolomics further confirmed that PTL affected amino acid metabolism in LUAD. Network pharmacology, molecular docking, and molecular dynamics simulations identified GCTG as a potential target of PTL in LUAD. Meanwhile, and experimental results indicated that PTL targeting GCTG affected the proliferation, amino acid metabolism, and oxidative stress levels of LUAD cells.

CONCLUSION

PTL affects proliferation, amino acid metabolism, and oxidative stress levels of LUAD cells via targeting GCTG. Therefore, our study provides new insights into the prevention and treatment of LUAD with PTL, which may lay the foundation for future research directions.

摘要

背景

肺腺癌(LUAD)每年在全球导致数百万人死亡。从传统中药中提取的小白菊内酯(PTL)具有多种生物学活性。在本研究中,我们研究了PTL对LUAD细胞中氨基酸代谢和氧化应激的影响。

方法

本研究通过无标记定量蛋白质组学和蛋白质-蛋白质相互作用网络,鉴定了PTL在LUAD细胞中的差异蛋白质和潜在作用机制。结合靶向氨基酸代谢组学,我们证实了基因本体(GO)和京都基因与基因组百科全书(KEGG)分析的结果。在此基础上,通过网络药理学、分子模拟对接和分子动力学模拟,确定了PTL在LUAD中的潜在靶点。最后,使用[具体实验名称1]和[具体实验名称2]实验验证了PTL对LUAD中氨基酸代谢和氧化应激的影响。

结果

PTL处理LUAD细胞导致157种蛋白质的表达发生显著变化。GO和KEGG富集分析表明,这些蛋白质参与氨基酸代谢和氧化应激反应。靶向氨基酸代谢组学进一步证实PTL影响LUAD中的氨基酸代谢。网络药理学、分子对接和分子动力学模拟确定GCTG为PTL在LUAD中的潜在靶点。同时,[具体实验名称1]和[具体实验名称2]实验结果表明,PTL靶向GCTG影响LUAD细胞的增殖、氨基酸代谢和氧化应激水平。

结论

PTL通过靶向GCTG影响LUAD细胞的增殖、氨基酸代谢和氧化应激水平。因此,我们的研究为PTL预防和治疗LUAD提供了新的见解,可能为未来的研究方向奠定基础。

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