In the present study, the inhibitory effects of zedoary turmeric oil (ZTO) on non‑small cell lung cancer (NSCLC) were investigated using integrated network pharmacology, molecular docking and in vitro experiments. Treatment with 100 µg/ml ZTO in A549 cells and 50 µM ZTO in H1299 cells markedly reduced cell viability (assessed through an MTT assay), suppressed proliferation (assessed through colony formation/EdU assays) and increased apoptosis (assessed through flow cytometry). Network analysis identified 27 bioactive components (such as curcumadione and zedoradiol) and 96 shared targets with NSCLC. Core targets (including ESR1, EGFR, PIK3CA and PIK3CB) were found to be enriched in the EGFR/PI3K/Akt signaling pathway. Molecular docking demonstrated stable binding between the ZTO components and these targets. Furthermore, reverse transcription‑quantitative PCR and western blotting revealed that ZTO downregulated ESR1 and EGFR expression (P<0.05). These findings suggested that ZTO suppressed NSCLC progression by modulating the EGFR/PI3K/Akt pathway, with its active components potentially targeting key oncogenic regulators. The present study therefore highlights the therapeutic potential of ZTO as a multi‑target agent against NSCLC.
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