肺腺癌是肺癌的主要病理类型。据报道，奇山方剂对肺腺癌有疗效，然而其作用机制目前仍不清楚。因此，本研究利用网络药理学、分子对接技术和蛋白质组学来验证奇山方剂在肺腺癌治疗中的潜在药理作用。利用中药系统药理学数据库、化学源网络和Cytoscape v3.7.2构建药物-成分-靶点网络，获取奇山方剂的活性成分和潜在靶点。从TCGA、OMIM、DrugBank、DisGeNET和GeneCards等5个数据库中获取疾病靶点数据，利用药物疾病交叉靶点构建蛋白质相互作用网络，并利用STRING数据库选择核心靶点和DAVID数据库构建富集通路网络。最后，利用TMT定量蛋白质组学鉴定可能的核心靶点和作用途径，并进行分子对接验证成分和靶点之间的亲和力。网络药理学鉴定出奇山方剂对肺腺癌的核心成分包括黄芩苷、甲基麝香草酮B、槲皮素、山奈酚、伊索酮和黄烷酮等，可作用于10个关键靶点（SRC、TP53、PIK3R1、MAPK3、STAT3、MAKP1、HSP90AA1、PIK3CA、HRAS和AKT1）。奇山方剂可能通过调节信号传导、蛋白质磷酸化、细胞增殖和凋亡等生物学过程以及PI3K/AKT、MAPK、FoxO和其他信号通路，在肺腺癌治疗中发挥治疗作用。蛋白质组学鉴定出207个差异表达蛋白质，结合网络药理学和分子对接结果，我们发现奇山方剂的6个核心成分可能通过PI3K/AKT信号通路靶向TP53，对肺腺癌产生作用。奇山方剂是一种多靶点配方，可能在肺腺癌中产生多效作用。版权所有 © 2023 作者。由 Wolters Kluwer Health, Inc. 发布。

Lung adenocarcinoma (LUAD) is the main pathological type of lung cancer. Qishan formula (QSF) is reportedly efficacious against LUAD. However, its mechanisms of action currently remain elusive. Therefore, network pharmacology, molecular docking techniques and proteomics were used to verify the potential pharmacological effects of QSF in the treatment of LUAD.The active ingredients and potential targets of QSF were obtained from the TCMSP, chemical source network and construct a drug-component-target networks using Cytoscape v3.7.2. Data for disease targets were obtained from 5 databases: TCGA, OMIM, DrugBank, DisGeNET, and GeneCards. Drug disease cross targets were used to construct protein-protein interaction networks for selecting the core targets using the STRING database and enrichment pathway networks using the DAVID database. Finally, TMT quantitative proteomics was used to identify the possible core targets and action pathways. Molecular docking to verify the affinity between components and targets.Network pharmacology identified core components of QSF against LUAD included baicalein, methylophiopogonone B, quercetin, kaempferol, isorhamnetin, and luteolin, which can act on 10 key targets (SRC, TP53, PIK3R1, MAPK3, STAT3, MAKP1, HSP90AA1, PIK3CA, HRAS, and AKT1). QSF might play a therapeutic role in LUAD by regulating biological processes such as signal transduction, protein phosphorylation, cell proliferation, and apoptosis, as well as the PI3K/AKT, MAPK, FoxO, and other signaling pathways. Proteomics identified 207 differentially expressed proteins, and by integrating with network pharmacology and molecular docking results we found that 6 core components of QSF may target TP53 against LUAD through the PI3K/AKT signaling pathway.QSF is a multitarget recipe potentially exerting pleiotropic effects in LUAD.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.