Mechanism of scopoletin regulates gefitinib resistance in lung cancer cells
[Objective]To explore the potential mechanism of Scopoletin regulating gefitinib resistance in non-small cell lung cancer cells.[Method]CCK-8 was used to detect PC in non-small cell lung cancer cells and Gefitinib resistant cells and to calculate Gefitinib semi-maximum inhibitory concentration(IC50)under Scopoletin treatment or no treatment.Molecular doc-king analysis of interactions between scopolamine and proteins potentially causing gefitinib resistance.The effects of scopolam-ine and FGL1 on the expression of proteins related to apoptosis and proliferation in tumor cells were analyzed by genetic meth-ods and Western Blotting.[Result]The IC50 of PC9/GR cells against gefitinib was 15.66 µmol/L.After Scopoletin treatment,the IC50 of PC9/GR cells against gefitinib was 1.81 µmol/L,respectively.The binding free energy between scopoletin and FGL1 was-18.44 kcal/mol,and the binding sites were T70,F96 and K150.After FGL1 knockdown,the resistance of PC9/GR cells to gefitinib decreased significantly,and IC50 decreased to 3.52 µmol/L.After Scopoletin treatment,the resistance of PC9/GR cells to gefitinib did not change significantly,regardless of overexpression or FGL1 knockdown.After FGL1 knockdown,p-EGFR expression levels decreased,Cleaved-PARP1 and Cleaved-caspase3 expression levels increased.[Conclusion]Scopo-letin reversed gefitinib resistance in non-small cell lung cancer cells by activating apoptosis pathway by targeting FGL1.
scopoletinFGL1non-small cell lung cancer cellsgefitinibdrug resistancemolecular dockingIC50
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