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通过网络分析和实验验证确定半夏泻心汤治疗胃癌的机制

Determining the Mechanism of Banxia Xiexin Decoction for Gastric Cancer Treatment through Network Analysis and Experimental Validation.

作者信息

Li Yaxing, Li Ling, Wang Xue, Huang Hailiang, Han Tao

机构信息

Pharmacology of Traditional Chinese Medical Formulas, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, China.

Rehabilitation Medicine and Physiotherapy, School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, China.

出版信息

ACS Omega. 2024 Feb 21;9(9):10119-10131. doi: 10.1021/acsomega.3c06330. eCollection 2024 Mar 5.


DOI:10.1021/acsomega.3c06330
PMID:38463316
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10918669/
Abstract

Gastric cancer (GC) is a widespread malignancy. Banxia Xiexin decoction (BXD) has been used for GC treatment, but the specific mechanisms underlying its therapeutic effects remain controversial. This study used a comprehensive approach to network pharmacology combined with experimental validation to elucidate the mechanism of BXD's anti-GC effects. Initially, we used the UHPLC-LTQ-Orbitrap-MS/MS technology to identify the main chemical constituents of BXD, as well as potential targets associated with these constituents. Then, we employed the Genecard and Online Mendelian Inheritance in Man (OMIM) to determine the targets specifically related to GC. We employed a combination of Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction analysis to predict the crucial targets of BXD and uncover the pathways involved in its therapeutic effects against GC. The results were subsequently verified through cell experiments. The analysis revealed 174 common targets shared by BXD and GC. GO enrichment analysis highlighted biological processes, such as autophagy, protein kinase activity, and apoptosis. Moreover, the enrichment analysis revealed several significant pathways that serve as the primary mechanisms by which BXD exerts its effects. Notably, these pathways include PI3K-Akt, HIF-1, and Pathways in cancer. Subsequent in vitro experiments demonstrated that BXD effectively hindered GC cell proliferation, stimulated autophagy, and facilitated apoptosis by PI3K-Akt-mTOR signaling pathway regulation. These findings reveal the effectiveness of BXD against GC through diverse components, targets, and pathways, indicating that BXD holds potential therapeutic value in GC treatment. This study uncovers the intricate biological mechanisms that underlie BXD's efficacy in treating GC through the integration of network pharmacology analysis and rigorous in vitro experiments.

摘要

胃癌(GC)是一种广泛存在的恶性肿瘤。半夏泻心汤(BXD)已用于胃癌治疗,但其治疗效果的具体机制仍存在争议。本研究采用网络药理学与实验验证相结合的综合方法,阐明BXD抗胃癌作用的机制。首先,我们使用超高效液相色谱-线性离子阱-轨道阱串联质谱(UHPLC-LTQ-Orbitrap-MS/MS)技术鉴定BXD的主要化学成分以及与这些成分相关的潜在靶点。然后,我们利用基因卡片(Genecard)和《人类孟德尔遗传在线》(OMIM)确定与胃癌特异性相关的靶点。我们结合基因本体论(GO)、京都基因与基因组百科全书(KEGG)通路以及蛋白质-蛋白质相互作用分析,预测BXD的关键靶点,并揭示其抗胃癌治疗作用所涉及的通路。随后通过细胞实验对结果进行验证。分析发现BXD和胃癌共有174个共同靶点。GO富集分析突出了自噬、蛋白激酶活性和细胞凋亡等生物学过程。此外,富集分析还揭示了几个作为BXD发挥作用主要机制的重要通路。值得注意的是,这些通路包括PI3K-Akt、HIF-1和癌症相关通路。随后的体外实验表明,BXD通过PI3K-Akt-mTOR信号通路调节有效抑制胃癌细胞增殖、刺激自噬并促进细胞凋亡。这些发现揭示了BXD通过多种成分、靶点和通路对胃癌的有效性,表明BXD在胃癌治疗中具有潜在的治疗价值。本研究通过网络药理学分析与严格的体外实验相结合,揭示了BXD治疗胃癌疗效背后复杂的生物学机制。

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