桑舒柳,丁蓉珍,姜靖洁,等.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[J].安徽医药,2023,27(8):1516-1520. |
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 |
Exploring the molecular mechanism of Feiyanning in the treatment of non-small cell lung cancer based on network pharmacology and experimental verification |
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DOI:10.3969/j.issn.1009-6469.2023.08.008 |
中文关键词: 癌,非小细胞肺 网络药理学 肺岩宁方 信号通路 |
英文关键词: Carcinoma,non-small-cell lung Network pharmacology Feiyanning Signaling pathway |
基金项目:国家自然科学基金资助项目( 82074339) |
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中文摘要: |
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 qP CR 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分析表明肺岩宁方通过 11种成分影响 71个重要靶点而发挥抗非小细胞肺癌作用,其中有 14个靶点与肺癌病人生存相关,可能与 PI3K-AKT等多种信号通路相关。肺岩宁方能抑制 HCC827细胞的增殖能力,克隆形成能力以及侵袭能力,并下调 PI3K-AKT信号通路的关键基因 KIT的 mRNA水平。结论肺岩宁方治疗 NSCLC的作用机制可能是通过下调 KIT调控 PI3K-AKT信号通路来实现的。 |
英文摘要: |
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. |
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