Abstract
Genetics, lifestyle, and hormones influence lung cancer, the most common malignancy in the world. VEGFR plays a key role in tumor growth and metastasis by promoting angiogenesis. While anti-angiogenic therapies targeting VEGFR show potential, resistance remains a challenge, and elevated VEGFR levels are associated with aggressive tumors and poor outcomes. This research explores using natural flavonoids to inhibit VEGFR activity in lung cancer, focusing on computational studies and in-vitro assays with the A549 cell line. Molecular docking revealed that 18 flavonoids outperformed axitinib and 26 surpassed sorafenib in effectiveness. Molecular dynamics simulation showed system stabilization after 80 ns with RMSD between 2 and 4 Å RMSF analysis revealed fluctuations in the activation loop and hinge region. Hydrogen bonds, especially with GLU 149, were key to the complex's stability. PCA highlighted conformational changes, and MM/GBSA calculated a binding free energy of -34.72 kcal/mol. In particular, quercetin had a lower IC50 value (6.24 ± 0.42 µM) than axitinib (7.85 ± 0.59 µM), which means it had stronger effects on lung cancer cells. Other flavonoids like taxifolin and luteolin showed similar efficacy. The findings suggest potential for tailored therapies that could enhance personalized treatment approaches for lung cancer.
Published Version
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