摘要
BACKGROUND Non-small cell lung cancer(NSCLC)is frequently characterized by poor response to cisplatin(DDP)-based chemotherapy,with increasing evidence suggesting that inflammatory cytokines in the tumor microenvironment contribute to chemoresistance.AIM To investigate the role of inflammatory cytokines in DDP resistance and to effect of IL-6 inhibition on chemosensitivity in NSCLC.METHODS Twenty NSCLC patients were grouped into DDP-sensitive or DDP-resistant cohorts based on their clinical response.Cytokine levels in tumor tissues and NSCLC cell lines,including DDP-resistant A549/DDP and SK-MES-1/DDP,were quantified using enzyme-linked immunosorbent assay.To verify the effects of interleukin(IL)-6 on DDP resistance,NSCLC and resistant cells were treated with IL-6 inhibitors tocilizumab(TCZ),followed by DDP treatment.Cell viability,apoptosis,migration and invasion were detected via cell counting kit-8,flow cytometry,scratch assay,and transwell,respectively.RESULTS IL-6,IL-8,and tumor necrosis factor-αlevels were significantly elevated in DDP-resistance tissues and cell models compared to sensitive controls(P<0.05).TCZ treatment significantly reduced the half-maximal inhibitory concentration of DDP in resistant cells,induced apoptosis,and hindered migration and invasion(P<0.05).IL-6 and IL-8 were identified as key cytokines associated with DDP resistance.CONCLUSION These findings demonstrated that IL-6 and related cytokines contribute to DDP resistance in NSCLC.IL-6 inhibition restores chemosensitivity and may serve as a promising therapeutic strategy in resistant NSCLC.
