The co-action mechanism of agreement prescription "homotherapy for heteropathy" against esophageal, head and neck cancer, and lung cancer: network pharmacology, bioinformatics analysis, and experimental validation.

[BACKGROUND] "Homotherapy for heteropathy" represents a distinctive therapeutic strategy informed by Traditional Chinese Medicine (TCM) principles. This study aims to explore the common targets and molecular mechanisms of the agreement prescription in the treatment of esophageal cancer, head and neck cancer and lung cancer using network pharmacology, bioinformatics and in vitro and in vivo experiments.

[METHODS] Active ingredients and targets of the prescription were screened via TCMSP, MelaCards, CTD, and Disgenet databases. Cancer-related genes were intersected with prescription targets. Protein-protein interaction (PPI) network was constructed with STRING. Hub targets were identified with Cytoscape. Molecular docking was performed with AutoDock. Expression/prognosis values of the targets across pan-cancer were analyzed using TCGA/UALCAN. Single-cell transcriptomics was employed to assess transcriptional changes and pathway enrichment post-treatment. Anti-cancer effects were validated through in vitro and in vivo experiments.

[RESULTS] Eight shared targets were identified, primarily enriched in the PI3K-AKT pathway. Molecular docking confirmed strong binding between VEGFA/CCR7 and components of the agreement prescription. These targets were overexpressed in pan-cancer and correlated with poor prognosis. Transcriptomic analysis revealed significant enrichment of differentially expressed genes (DEGs) in the PI3K-AKT pathway after treatment. In vitro, the prescription inhibited cancer cell proliferation and migration while promoting apoptosis, accompanied by downregulation of CCR7, VEGFA, and PI3K-AKT signaling. In vivo, tumor growth was suppressed and VEGFA/CCR7 expression in tumor tissues was reduced.

[CONCLUSION] The common targets of the agreement prescription in treating esophageal cancer, head and neck cancer, and lung cancer may include CCR7, VEGFA, and the PI3K-AKT pathway, thereby exerting its anti-cancer effects.