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

  • World J Clin Oncol. 2025 Oct 24;16(10):112097. doi: 10.5306/wjco.v16.i10.112097.
Yue Dai  1 ,  Ya-Yun Liu  2 ,  Nian Cao  1 ,  Xiu-Wen Tian  1 ,  Juan Feng  1 ,  Zhen-Zhen Hu  1 ,  Jian-Qiang Xu  3
Affiliations
  • 1. Department of Pulmonary and Critical Care Medicine, The Third Clinical Medical College of the Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang 443002, Hubei Province, China.
  • 2. Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, Hubei Province, China.
  • 3. Department of Pulmonary and Critical Care Medicine, The Third Clinical Medical College of the Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang 443002, Hubei Province, China. [email protected].
PMID: 41178924 DOI: 10.5306/wjco.v16.i10.112097
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.

Keywords
Chemotherapy sensitivity; Cisplatin; Inflammatory cytokines; Non-small cell lung cancer; Tumor microenvironment.
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