Work

Overcoming chemoresistance in non-small cell lung cancer: Insights into the influence of inflammatory factors on treatment response

Year: 2025

Type: article

Abstract: 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-α levels 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.

Source: World Journal of Clinical Oncology

DOI: 10.5306/wjco.v16.i10.112097