Ginsenoside CK ameliorates tumor growth in lung cancer mice via inhibiting EGFR

• Ginsenoside CK may serve as a potential EGFR tyrosine kinase inhibitor. • Ginsenoside CK suppresses the proliferation and induces the apoptosis of A549 cells. • Ginsenoside CK combined with gefitinib shows better inhibitory effect of tumor growth in mice. • Ginsenoside CK elicits anti-lung cancer effect via the EGFR/MAPK/ERK signaling pathway. In this work, ginsenoside CK was confirmed as an EGFR tyrosine kinase inhibitor, with an IC 50 value of 32.58 ± 0.09 μM. Molecular docking showed that ginsenoside CK could fit into EGFR binding pocket, thereby acting as a ligand for EGFR. Ginsenoside CK inhibited proliferation of A549 cells as well as induced its apoptosis via downregulating anti-apoptotic factors and upregulating apoptosis induction factors. Ginsenoside CK alone and combined with gefitinib inhibited the tumor progression of A549 lung cancer xenografts in BALB/c nude mice. ELISA assay showed that ginsenoside CK combined with gefitinib alleviated the inflammatory response by suppressing the release of pro-inflammatory cytokines, indicating better inhibitory effects than ginsenoside CK or gefitinib alone. This work further confirmed that ginsenoside CK regulated the EGFR/MAPK/ERK signaling both in vitro and in vivo . In conclusion, ginsenoside CK can exhibit the anti-lung cancer effect via acting as an EGFR tyrosine kinase inhibitor.