文章摘要
周仕敏,谭雅琴,张丽,等.基于网络药理学和实验验证探究左归丸抑制头颈部鳞状细胞癌的作用机制[J].安徽医药,2024,28(7):1312-1317.
基于网络药理学和实验验证探究左归丸抑制头颈部鳞状细胞癌的作用机制
Mechanism of Zuoguiwan in inhibiting head and neck squamous cell carcinoma based on network pharmacology and experimental verification
  
DOI:10.3969/j.issn.1009-6469.2024.07.009
中文关键词: 左归丸  头颈鳞癌  网络药理学  分子对接  作用机制
英文关键词: Zuoguiwan  Head and neck squamous cell carcinoma  Network pharmacology  Molecular docking  Mechanism of action
基金项目:湖北省教育厅科学技术研究项目( Q20222114)
作者单位
周仕敏 国药东风茅箭医院口腔科湖北十堰 442000 
谭雅琴 湖北医药学院附属太和医院口腔科湖北十堰 442000 
张丽 湖北医药学院附属太和医院口腔科湖北十堰 442000 
邓志鹏 湖北医药学院附属太和医院口腔科湖北十堰 442000 
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中文摘要:
      目的基于网络药理学和体外实验探究左归丸作用于头颈部鳞状细胞癌( HNSCC)的靶点并分析潜在机制。方法自 2022年 11月至 2023年 3月分别通过 TCMSP、BATMAN-TCM、GeneCards、CTD、OMIM数据库筛选左归丸的活性成分并筛选左归丸作用于 HNSCC的潜在靶点;使用 String数据库构建潜在靶点互作网络,并进行多步拓扑分析筛选出核心靶点;使用 DAVID和 Metascape数据库对潜在靶点进行富集分析;最后运用 Auto Dock Vina进行核心成分与靶点的分子对接并通过细胞计数试剂盒(CCK-8)、蛋白质印迹法验证左归丸对 HNSCC的治疗作用及机制。结果左归丸的 8种活性成分具有 487个药物靶点,其中 440个为 HNSCC相关基因;两步拓扑结构分析得到表皮生长因子( EGFR)、细胞周期蛋白 D1(CCND1)、热休克蛋白 90α家族 A类成员 1(HSP90AA1)、核因子 kappa B激酶亚基 β抑制剂( IKBKB)和螺旋环螺旋结构域扩散激酶( CHUK)5个核心靶点;富集结果提示左归丸通过影响多种生物学功能和信号通路在 HNSCC中发挥作用;分子对接结果显示,左归丸与核心靶点之间结合稳定。体外实验显示,与对照组相比,左归丸处理组显著抑制了 WSU-HN6和 CAL-27细胞增殖能力( P<0.001)并且可以降低 CCND1,IKBKB和 CHUK(P<0.05)的蛋白表达水平。结论左归丸能够靶向多条促癌信号通路从而对 HNSCC起到抑制作用。
英文摘要:
      Objective To identify the targets of Zuoguiwan (ZGW) on head and neck squamous cell carcinoma (HNSCC) and to explore the potential mechanism based on network pharmacology and in vitro experiments.Methods From November 2022 to March 2023, TCMSP, BATMAN-TCM, GeneCards, CTD and OMIM were employed to analyze the active components of ZGW and to screenthe potential targets of ZGW on HNSCC. String database was used to construct an interaction network for potential targets, and the coretargets were obtained via multiple step topology analysis. The DAVID and Metascape databases were used for enrichment analysis ofthe potential targets. Finally, molecular docking between core components and targets was performed by Auto Dock Vina, and CCK-8 and Western blot were used to verify the therapeutic effect and mechanism of ZGW on HNSCC.Results The 8 active components with 487 drug targets were screened out, 440 of which were HNSCC-related genes. Two-step topological data analysis results showed thatepidermal growth factor receptor (EGFR), cyclin D1 (CCND1), heat shock protein 90 alpha family class A member 1 (HSP90AA1), inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) and component of inhibitor of nuclear factor kappa B kinase complex(CHUK) were the core target genes. The enrichment analysis results suggested that ZGW played a role in HNSCC by regulating variousbiological functions and signaling pathways. Molecular docking results showed that ZGW docked well with core targets. In vitro experi ment results showed that compared with the control group, ZGW treatment groups significantly inhibited the proliferation ability ofWSU-HN6 and CAL-27 cells (P<0.001) and reduced the protein expression levels of CCND1, IKBKB and CHUK(P<0.05).Conclu- sion ZGW can target multiple cancer-promoting signaling pathways to inhibit the progression of HNSCC.
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