Liu Xing, Wang Kesheng, Wang Luling, Fan Xingliang
Department of Central Laboratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, 200072, China.
J Cancer. 2023 Feb 13;14(4):505-518. doi: 10.7150/jca.76591. eCollection 2023.
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.
对肝细胞癌(HCC)有效;然而,其潜在的作用机制仍不清楚。本研究旨在探讨其作用的潜在机制以及各成分对HCC的影响。首先,研究了其对HCC的影响以及……。在……实验中,用不同浓度(0、1、2mg/mL)的溶液处理HCC细胞系,然后评估细胞凋亡、增殖、迁移、侵袭和血管生成能力。在……实验中,将24只小鼠随机分为以下四组:模型组以及低、中、高剂量组。评估肿瘤生长以及CD34和Ki67表达水平,以确定其对细胞增殖和血管生成能力的影响。此外,利用转录组测序和差异表达分析来鉴定其在HCC细胞中诱导的差异表达基因(DEG)。另外,进行质谱分析以鉴定其化学成分。使用四个数据库预测这些化学成分在HCC中的靶蛋白。从两个数据库中鉴定出HCC相关基因。通过对鉴定出的DEG、靶蛋白和HCC相关基因进行交叉分析,确定了关键的其调控的HCC相关基因。随后,利用蛋白质-蛋白质相互作用网络、网络药理学和分子对接来鉴定其中的活性化合物及其可能的基因靶点。……实验表明其诱导肿瘤细胞凋亡并抑制细胞增殖、迁移、侵袭和血管生成潜能。……实验表明其以剂量依赖性方式抑制肿瘤生长。生物信息学分析鉴定出49个关键调控的HCC相关基因,其中……、……、……和……最为显著。质谱分析在其中鉴定出以下五种具有潜在抗HCC活性的分子:4',5,7-三羟基黄酮;原儿茶酸乙酯;3,5-二羟基苯甲酸;仙茅皂苷A;和仙茅苷G。分子对接验证了其中活性化合物与HCC中靶蛋白之间的相互作用。本研究证实了其对HCC的治疗作用,并鉴定出可能有助于其作用机制的关键基因和活性成分,从而为进一步研究HCC的靶向治疗提供了依据。