Han Yang, Jiao Lijing, Zhou Hailun, Sang Shuliu, A Geer, Liu Ruichao, Du Yizhao, Wang Mengqi, Kang Xiaohong, Wang Qin, Gong Yabin
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
Department of Radiotherapy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453000, China.
J Ethnopharmacol. 2025 Jul 24;351:120120. doi: 10.1016/j.jep.2025.120120. Epub 2025 Jun 9.
Drug resistance in lung cancer poses a significant challenge in clinical treatment. Feiyanning formula (FYN) is a traditional Chinese medicine formula developed through years of clinical practice. However, the specific mechanisms by which FYN and its extract inhibit drug resistance in lung cancer remain unclear.
This study aims to elucidate the therapeutic potential and underlying molecular mechanisms of FYN and its extract in the treatment of lung cancer.
To explore how FYN interacts with potential targets in treating non-small cell lung cancer (NSCLC), a comprehensive strategy was employed, including network pharmacology, ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS), cellular assays, animal models, and molecular docking. Protein-protein interaction (PPI) network construction and functional analysis were used to investigate how FYN and its extract, apigenin, may overcome resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The molecular mechanisms were further validated using an NSCLC resistance animal model.
The study confirmed that FYN and its extract inhibit the proliferation, migration, and invasion of H1975OR cells. Using network pharmacology and UPLC-HRMS, shared components between the FYN formula and drug-containing serum were identified, and a potential target network related to NSCLC resistance was constructed. Gene enrichment analysis indicated that FYN targets the IGF1R-PI3K-Akt signaling pathway in combating NSCLC resistance. Molecular docking revealed interactions between FYN's extract and key pathway-related genes. Cell phenotype assays showed that FYN not only suppresses proliferation, migration, and invasion of resistant NSCLC cells but also induces apoptosis and promotes cell cycle arrest. Additionally, animal experiments demonstrated that FYN significantly inhibits the growth of H1975OR xenografts in nude mice. Western blot analysis suggested that FYN may suppress the IGF1R-PI3K-Akt pathway in vivo.
This study explores the pharmacological effects and underlying mechanisms of FYN and its extract, apigenin, in the treatment of drug-resistant NSCLC. The findings support the therapeutic efficacy of FYN as a potential clinical treatment for lung cancer and provide robust scientific evidence for further investigation into the mechanisms of osimertinib resistance and the action of FYN.
肺癌中的耐药性给临床治疗带来了重大挑战。肺岩宁方（FYN）是经过多年临床实践研制出的中药方剂。然而，FYN及其提取物抑制肺癌耐药性的具体机制仍不清楚。
本研究旨在阐明FYN及其提取物在肺癌治疗中的治疗潜力和潜在分子机制。
为探究FYN在治疗非小细胞肺癌（NSCLC）中如何与潜在靶点相互作用，采用了一种综合策略，包括网络药理学、超高效液相色谱-高分辨率质谱联用（UPLC-HRMS）、细胞实验、动物模型和分子对接。利用蛋白质-蛋白质相互作用（PPI）网络构建和功能分析来研究FYN及其提取物芹菜素如何克服对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）的耐药性。使用NSCLC耐药动物模型进一步验证分子机制。
研究证实FYN及其提取物可抑制H1975OR细胞的增殖、迁移和侵袭。通过网络药理学和UPLC-HRMS，鉴定出FYN方剂与含药血清之间的共同成分，并构建了与NSCLC耐药相关的潜在靶点网络。基因富集分析表明，FYN在对抗NSCLC耐药性时靶向IGF1R-PI3K-Akt信号通路。分子对接揭示了FYN提取物与关键通路相关基因之间的相互作用。细胞表型实验表明，FYN不仅能抑制耐药NSCLC细胞的增殖、迁移和侵袭，还能诱导细胞凋亡并促进细胞周期停滞。此外，动物实验表明FYN能显著抑制裸鼠体内H1975OR异种移植物的生长。蛋白质免疫印迹分析表明FYN可能在体内抑制IGF1R-PI3K-Akt通路。
本研究探讨了FYN及其提取物芹菜素在治疗耐药NSCLC中的药理作用和潜在机制。研究结果支持FYN作为肺癌潜在临床治疗药物的治疗效果，并为进一步研究奥希替尼耐药机制和FYN的作用提供了有力的科学证据。
