Sang Shuliu, Han Yang, Zhou Hailun, Kang Xiaohong, Gong Yabin
Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Cancer Cell Int. 2025 Mar 15;25(1):99. doi: 10.1186/s12935-025-03690-5.
Fei Yanning Formula (FYN) is extensively applied in clinical lung cancer treatment. However, the specific active constituents and targets of its therapeutic effects remain unclear.
The study aims to explore the active constituents and mechanism of FYN in delaying osimertinib resistance by network pharmacology analysis and experimental verification.
We collected the chemical constituents of the FYN based on the TCMSP database and relevant literature sources. Osimertinib resistance-related targets were acquired from the GeneCards database. We systematically construct the PPI network and KEGG analysis to explore hub targets and key pathways. The main active components of FYN were identified by molecular docking. Subsequently, we conducted in vitro experiments to verify its effect on osimertinib-resistant cells in lung cancer.
The PPI network and KEGG pathways analysis revealed six key targets linked to PI3K-AKT signaling pathways (ERBB2, EGFR, MET, HSP90AA1, MCL1, and IGF1R). RT-qPCR and immunohistochemical analyses demonstrated that FYN could suppress the expression of ERBB2, MET and HSP90AA1. Molecular docking indicated that Ethyl caffeate, the primary component in FYN, had a stronger binding ability with MET. Experiments illustrated that Ethyl caffeate inhibited the migration and proliferation of osimertinib-resistant cells, promoted apoptosis, and suppressed the expression level of MET.
FYN might delay osimertinib resistance by downregulating the expression of MET, which can be attributed to its active ingredient, Ethyl caffeate.
肺岩宁方（FYN）在肺癌临床治疗中广泛应用。然而，其治疗效果的具体活性成分和靶点仍不明确。
通过网络药理学分析和实验验证，探索肺岩宁方延缓奥希替尼耐药的活性成分及作用机制。
基于中药系统药理学数据库（TCMSP）和相关文献来源收集肺岩宁方的化学成分。从基因卡片数据库获取奥希替尼耐药相关靶点。系统构建蛋白质-蛋白质相互作用（PPI）网络并进行京都基因与基因组百科全书（KEGG）分析，以探索核心靶点和关键通路。通过分子对接鉴定肺岩宁方的主要活性成分。随后，进行体外实验验证其对肺癌奥希替尼耐药细胞的作用。
PPI网络和KEGG通路分析揭示了与磷脂酰肌醇-3-激酶-蛋白激酶B（PI3K-AKT）信号通路相关的6个关键靶点（ERBB2、表皮生长因子受体（EGFR）、间质表皮转化因子（MET）、热休克蛋白90α家族成员1（HSP90AA1）、髓细胞白血病-1（MCL1）和胰岛素样生长因子1受体（IGF1R））。逆转录-定量聚合酶链反应（RT-qPCR）和免疫组化分析表明，肺岩宁方可抑制ERBB2、MET和HSP90AA1的表达。分子对接表明，肺岩宁方中的主要成分咖啡酸乙酯与MET具有更强的结合能力。实验表明，咖啡酸乙酯抑制奥希替尼耐药细胞的迁移和增殖，促进细胞凋亡，并抑制MET的表达水平。
肺岩宁方可能通过下调MET的表达来延缓奥希替尼耐药，这可能归因于其活性成分咖啡酸乙酯。
