Baicalin inhibits A549 cells proliferation and EMT through targeting the EGFR pathway.

[BACKGROUND] The high global incidence and mortality rates of lung cancer present a persistent worldwide health challenge. In this context, the epidermal growth factor receptor (EGFR) oncogene and the epithelial-mesenchymal transition (EMT) process are heavily implicated in tumor progression and invasiveness. Although the plant-Scutellaria baicalensis-derived flavonoid glycoside Baicalin potently suppresses lung cancer cell growth, its specific roles in modulating the EGFR signaling axis and EMT remain to be elucidated.

[METHODS] First, using the MTT assay and EdU staining, we determined the viability of A549 cells after exposure to varying concentrations of Baicalin (6.25, 12.5, 25, 50, 100 μM) for 24 or 48 h. Next, integrating network pharmacology with single-cell RNA sequencing (scRNA-seq) analysis screened for potential genes between Baicalin and lung cancer. Subsequently, the upregulation and downregulation of EMT markers and EGFR in Baicalin-treated A549 cells was assessed by immunofluorescence staining and RT-qPCR. Additionally, the EGFR agonist EGF and the inhibitor Canertinib were applied to further validate the findings.

[RESULTS] Baicalin exerted dose- and time-dependent anti-proliferative effects on A549 cells. The EGFR gene was selected through the combined application of network pharmacology and single-cell sequencing. RT-qPCR and immunofluorescence staining indicated that Baicalin inhibited the expression of EGFR and the progression of EMT. In addition, Baicalin inhibited EGF-induced migration of A549 cells. The inhibitory effect was even more pronounced when combined with Canertinib, collectively demonstrating a strong anti-migratory potential.

[CONCLUSIONS] Baicalin suppresses A549 cell proliferation and EMT via inhibiting the activation of the EGFR signaling pathway.