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IL-7-Mediated IL-7R-JAK3/STAT5 signalling pathway contributes to chemotherapeutic sensitivity in non-small-cell lung

Lin Shi1, Zhaozhong Xu2, Qiong Yang3

  • 1Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China.

Cell Proliferation
|October 11, 2019
PubMed
Abstract

Insights

Interleukin-7 (IL-7) enhances non-small-cell lung cancer (NSCLC) sensitivity to cisplatin by activating the IL-7 receptor-JAK3/STAT5 pathway. This combination therapy shows significant anti-tumour efficacy in vivo.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Chemotherapy resistance is a significant hurdle in treating non-small-cell lung cancer (NSCLC).
  • Combining immunotherapy with chemotherapy presents a promising strategy for cancer treatment.
  • Interleukin-7 (IL-7) is being investigated for its potential role in modulating cancer cell response to therapy.

Purpose of the Study:

  • To evaluate the anti-tumour efficacy of combining IL-7 with cisplatin in NSCLC.
  • To elucidate the molecular mechanisms underlying the combined therapeutic effect.

Main Methods:

  • Cell proliferation and apoptosis assays (CCK-8, EdU, colony-forming, HOECHST 33342, flow cytometry).
  • Western blot analysis for protein expression.
  • Inhibition of IL-7 receptor (IL-7R), JAK3, and STAT5 to investigate signalling pathways.
  • In vivo xenograft model to assess therapeutic effects.

Main Results:

  • IL-7R expression was elevated in cisplatin-resistant NSCLC cells (A549/DDP).
  • Blocking IL-7R reversed the combined inhibitory effects of IL-7 and cisplatin and reduced cisplatin-induced apoptosis.
  • The JAK3/STAT5 signalling pathway was identified as crucial for IL-7-mediated enhancement of cisplatin sensitivity.
  • In vivo studies demonstrated that the combination of IL-7 and cisplatin achieved the best therapeutic effect, significantly inhibiting tumour growth.

Conclusions:

  • IL-7 promotes NSCLC cell sensitivity to cisplatin through the IL-7R-JAK3/STAT5 signalling pathway.
  • The combination of IL-7 and cisplatin holds significant therapeutic potential for NSCLC treatment.
Keywords:
IL-7IL-7RJAK3NSCLCSTAT5cisplatin resistance

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