消炎中汤通过调节MAPK和PI3K-AKT信号通路抑制胃癌进展，提高5-Fu疗效

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2025-05-26 DOI:10.1016/j.jchromb.2025.124671

Yanxue Xu , Yumeng Zhang , Chen Huang , Min Zhao , Yihe Huang

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引用次数: 0

摘要

本研究旨在探讨消炎中汤（XJZD）增强氟尿嘧啶（5-Fu）治疗胃癌（GC）的药理机制。材料与方法采用网络药理学方法，对泻泻散治疗GC的作用途径进行评价。网络药理学分析结果通过MTT、流式细胞术、qPCR和ELISA实验验证。此外，代谢组学被用于鉴定差异代谢物并阐明所涉及的主要代谢途径。结果xjjzd抑制GC-803细胞增殖，诱导细胞凋亡。XJZD与5-Fu联合显著上调JNK1、JNK2 mRNA水平，下调ERK1、ERK2和p38 mRNA水平。此外，XJZD +5-Fu治疗降低了GC-803细胞中PI3K、AKT和mTOR的表达，提示XJZD通过诱导凋亡和调节MAPK和PI3K-AKT信号通路来增强5-Fu的治疗效果。代谢组学分析确定了16种主要影响氨基酸和能量代谢的关键代谢物。结论本研究通过网络药理学、体外验证、代谢组学等方法，确定了XJZD联合5-Fu治疗GC的潜在治疗途径。XJZD治疗GC的机制涉及多种有效成分、靶点和信号通路的协同作用，以及氨基酸和能量代谢的调节作用。本研究结果为中药复方XJZD联合5-Fu治疗GC的药理机制提供了新的认识。

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Xiaojianzhong decoction inhibits gastric cancer progression and enhances 5-Fu efficacy by regulating the MAPK and PI3K-AKT signaling pathway

Aim of the study

This study aims to investigate the pharmacological mechanisms underlying the enhancement of fluorouracil (5-Fu) efficacy by Xiaojianzhong decoction (XJZD) in the treatment of gastric cancer (GC).

Materials and methods

Network pharmacology was utilized to assess the therapeutic pathways of XJZD in the treatment of GC. The results from the network pharmacology analysis were validated through MTT assays, flow cytometry, qPCR, and ELISA experiments. Additionally, metabolomics was applied to identify differential metabolites and clarify the primary metabolic pathways involved.

Results

XJZD inhibited the proliferation of GC-803 cells and induced apoptosis. Furthermore, the combination of XJZD with 5-Fu significantly upregulated the mRNA levels of JNK1, JNK2, while downregulating the mRNA levels of ERK1, ERK2 and p38. Additionally, XJZD +5-Fu treatment reduced the expression of PI3K, AKT, and mTOR in GC-803 cells, suggesting that XJZD enhances the therapeutic effect of 5-Fu by inducing apoptosis and modulating the MAPK and PI3K-AKT signaling pathways. Metabolomics analysis identified 16 key metabolites that primarily influence amino acid and energy metabolism.

Conclusions

In this study, the potential therapeutic pathway of XJZD in combination with 5-Fu for the treatment of GC was identified through network pharmacology, in vitro validation, and metabolomics. The therapeutic mechanism of XJZD in GC involves the synergistic effects of multiple active ingredients, targets, and signaling pathways, as well as the modulation of amino acid and energy metabolism. These findings provide new insights into the pharmacological mechanisms underlying the combination of XJZD and 5-Fu in the treatment of GC.

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.