Network Pharmacology Combined with Experimental Validation Reveals the Anti-tumor Effect of Duchesnea indica against Hepatocellular Carcinoma.

Journal of Cancer(2023)

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摘要
is effective against hepatocellular carcinoma (HCC); however, its underlying mechanism of action remains unclear. The present study aimed to investigate the potential mechanism of action and effects of components against HCC. First, the effects of against HCC were investigated and . For experiments, HCC cell lines were treated with solutions at different concentrations (0, 1, 2 mg/mL) and then assessed for cell apoptosis, proliferation, migration, invasion, and angiogenic ability. For experiments, 24 mice were randomly divided into the following four groups: model group and low-, medium-, and high-dose groups. Tumor growth and CD34 and Ki67 expression levels were assessed to determine the effects of on cell proliferation and angiogenic ability. Furthermore, transcriptome sequencing and differential expression analyses were used to identify -induced differentially expressed genes (DEGs) in HCC cells. Additionally, mass spectrometry was conducted to identify the chemical components of . Four databases were used to predict the target proteins of these chemical components in HCC. HCC-associated genes were identified from two databases. By intersecting the identified DEGs; target proteins; and HCC-associated genes, key -regulated HCC-related genes were identified. Subsequently, protein-protein interaction network, network pharmacology, and molecular docking were used to identify the active compounds in and their likely gene targets. experiments demonstrated that induced tumor cell apoptosis and inhibited cell proliferation, migration, invasion, and angiogenic potential. experiments demonstrated that inhibited tumor growth in a dose-dependent manner. Bioinformatic analyses identified 49 key regulated HCC-related genes, of which , , , and were the most significant. Mass spectrometry identified the following five molecules in with potential anti-HCC activity: 4', 5, 7-trihydroxyflavone; ethyl protocatechuate; 3, 5-dihydroxy-benzoic acid; curculigosaponin A; and curculigine G. Molecular docking validated the interaction between active compounds and their target proteins in HCC. The present study confirmed the therapeutic effects of against HCC and identified the key genes and active components that may contribute to its mechanism of action, thereby providing a basis for further research on targeted therapeutics for HCC.
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关键词
Duchesnea indica,angiogenesis,hepatocellular carcinoma,metabolism,tumorigenesis
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