Effects and mechanisms of CCL2 in gefitinib resistance of non-small cell lung cancer

AimTo investigate the effects and the associated signaling mechanisms of C-C motif chemokine ligand 2 (CCL2) in gefitinib resistance of non-small cell lung cancer (NSCLC).MethodsBy using gefitinib-sensitive NSCLC strain PC9 and the corresponding drug-resistant strain PC9/GR as cell models, the expression of CCL2 in these two cell lines was compared. PC9 cells were pretreated with recombinant human CCL2 protein (rhCCL2), PC9/GR cells were subjected to siRNA-mediated knockdown of CCL2 gene or treatment with the CCL2 inhibitor Bindarit, and drug sensitivity to gefitinib was detected by CCK-8 assay. The biological signaling pathways involved in CCL2 were identified using gene set enrichment analysis (GSEA), and the expression of relevant signaling proteins was subsequently detected by knockdown of CCL2 in drug-resistant cells PC9/GR.ResultsBoth CCL2 mRNA and protein levels were significantly higher in PC9/GR cells than in PC9 cells (P P CCL2 or Bindarit exhibited significantly increased sensitivity to gefitinib (P ConclusionCCL2 is involved in gefitinib resistance in NSCLC by activating PI3K/AKT, JAK/STAT3, and RAS/ERK-related signaling pathways.