基于网络药理学与实验验证探讨肺岩宁方治疗非小细胞肺癌机制

目的 通过网络药理学筛选肺岩宁方治疗非小细胞肺癌（NSCLC）的潜在靶点和相关通路并通过实验验证其可能的作用机制。方法 检索TCMSP数据库和相关文献,获取肺岩宁方的有效化学成分和潜在作用靶点,查询Genecards、DisGeNET疾病数据库预测非小细胞肺癌疾病相关靶点。以非小细胞肺癌疾病靶点与肺岩宁方潜在作用靶点的交集靶点作为研究对象,采用Cytoscape 3.7.2软件构建活性成分-靶点网络图。利用STRING数据库构建蛋白质-蛋白质相互作用网络图,通过设置拓扑参数筛选出肺岩宁方治疗非小细胞肺癌的重要靶点,进行GO和KEGG分析,通过GEPIA数据库得到与肺癌病人生存相关的核心靶点。制备不同浓度的肺岩宁方干预HCC827细胞,采用CCK8法检测细胞增殖情况并计算IC50;平板克隆形成实验检测肺岩宁方对HCC827细胞克隆形成能力的影响;Transwell侵袭实验检测肺岩宁方对HCC827细胞侵袭能力的抑制作用。采用qPCR array技术检测网络药理学预测的核心靶点mRNA的表达水平。结果 肺岩宁方共有133个活性成分、521个相关靶点作用于非小细胞肺癌,GO和KEGG分析表明...

Exploring the molecular mechanism of Feiyanning in the treatment of non-small cell lung cancer based on network pharmacology and experimental verification

Objective To screen the potential targets and related pathways of Feiyanning in the treatment of non-small cell lung cancer (NSCLC) through network pharmacology, and to verify its possible mechanism of action by experiments.Methods The bioac tive compounds and potential targets of Feiyanning were obtained by the TCMSP database and related literatures. The targets related toNSCLC were predicted by the Genecards database and DisGeNET database. The intersection target of non-small cell lung cancer dis ease target and the potential action target of Feiyanning was selected as the study object. The active ingredient-target network map was constructed by Cytoscape 3.7.2 software. A protein-protein interaction (PPI) network map was developed by using the STRING data base, and the core targets of Feiyanning in the treatment of NSCLC were screened by setting topology parameters to perform GO andKEGG analysis.Core targets associated with the survival of lung cancer patients were identified through the GEPIA database. HCC827cells were treated with different concentrations of Feiyanning. The cell proliferation was detected by CCK8, and IC50 was calculated. The colony formation assay was performed to detect the effect of Feiyanning on the clone formation ability of HCC827 cells. Transwell assay was performed to detect the inhibition effect of Feiyanning on the invasion ability of HCC827 cells. qPCR array technique wasused to explore the expression levels of mRNA of core targets predicted by network pharmacology.Results There were 133 bioactive compounds and 521 relevant targets acting on NSCLC in Feiyanning. GO and KEGG analysis showed that Feiyanning exerted anti-NSCLC effects by influencing 71 important targets with 11 components, among which 14 targets were associated with the survival oflung cancer patients, possibly related to various signaling pathways such as PI3K-AKT. Feiyanning inhibited the proliferation, clonality, and invasion ability of HCC827 cells, and suppressed the mRNA of KIT which was the key gene in the PI3K-AKT pathway.Conclu sion The action mechanism of Feiyanning in the treatment of NSCLC may be realized by down-regulating KIT to regulate the PI3KAKT signaling pathway.