Investigating the Mechanism of Qingjie Yifei Miao Fang in Synergistic Treatment of Non-Small Cell Lung Cancer with Gefitinib Based on Network Pharmacology, In Vitro and In Vivo Experiments

Abstract

Objective: The aim of this study was to investigate the mechanism of Qingjieyifei Miao Fang (QJYFMF) in combination with gefitinib (GE) against non-small cell lung cancer (NSCLC). Methods: Network pharmacology was used to identify the key targets and signaling pathways of QJYFMF in the treatment of NSCLC. Both in vitro (A549 cell culture model) and in vivo (mouse lung cancer xenograft model) models were established. The therapeutic effects of QJYFMF on NSCLC were evaluated using CCK-8, flow cytometry, wound healing, and transwell assays. The expression of key proteins in the PTEN/PI3 K/AKT signaling pathway was assessed by Western blot and qRT-PCR. Results: A total of 98 active components and 901 targets of QJYFMF were identified, with the majority involved in the PI3K-AKT, MAPK, and apoptosis signaling pathways. Compared with the control group, QJYFMF significantly inhibited A549 cell proliferation, promoted apoptosis, and reduced cell migration and invasion abilities. In vivo, the transplanted tumor volume and weight were reduced, while the protein expression levels of PTEN, caspase-9, and BAD were increased. Additionally, the levels of PI3 K/p-PI3 K, AKT/p-AKT, p-caspase-9, and p-BAD were decreased, and the mRNA expression levels of BAD and caspase-9 were increased. The combination of GE and QJYFMF showed greater efficacy. Conclusion: QJYFMF significantly inhibited NSCLC proliferation, migration, and invasion while promoting apoptosis. The combination of GE and QJYFMF enhances the therapeutic effects of GE, potentially through the modulation of the PTEN/PI3 K/AKT signaling pathway.