Harmine suppresses the malignant phenotypes of Lewis lung carcinoma cells by inhibiting EGFR phosphorylation.

OBJECTIVE: To investigate whether harmine (HM) suppresses the malignant phenotypes of Lewis lung carcinoma (LLC) cells through an epidermal growth factor receptor (EGFR) -mediated mechanism. METHODS: Possible targets of HM and LLC-related genes were obtained from public databases, and overlapping targets were identified. A protein-protein interaction (PPI) network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was performed to predict the binding mode of HM with EGFR. The expression of phosphorylated EGFR (p-EGFR) was examined in LLC cells. In vitro assays were used to evaluate the effects of HM on cell viability, proliferation, colony formation, migration, invasion, and apoptosis. EGFR overexpression was further applied to assess whether EGFR was involved in the effects of HM. RESULTS: A total of 121 overlapping targets between HM and LLC were identified, and EGFR was recognized as a core hub target in the PPI network. Molecular docking predicted that HM could fit into the ATP-binding pocket of EGFR, with a binding energy below -7.0 kcal/mol. In LLC cells, HM showed selective cytotoxicity and significantly inhibited EGFR phosphorylation. HM also reduced cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. These effects were partially reversed by EGFR overexpression. CONCLUSION: HM suppresses the malignant phenotypes of LLC cells, at least in part, by inhibiting EGFR phosphorylation and EGFR-mediated signaling.