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

OBJECTIVES: The chemotherapy drug resistance is a major challenge for non‐small‐cell lung cancer (NSCLC) treatment. Combination of immunotherapy and chemotherapy has shown promise for cancer. The goal of this study was to evaluate the anti‐tumour efficacy of interleukin‐7 (IL‐7) combining cisplatin...

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Detalles Bibliográficos
Autores principales: Shi, Lin, Xu, Zhaozhong, Yang, Qiong, Huang, Yuanyuan, Gong, Yuxin, Wang, Fang, Ke, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869130/
https://www.ncbi.nlm.nih.gov/pubmed/31599032
http://dx.doi.org/10.1111/cpr.12699
Descripción
Sumario:OBJECTIVES: The chemotherapy drug resistance is a major challenge for non‐small‐cell lung cancer (NSCLC) treatment. Combination of immunotherapy and chemotherapy has shown promise for cancer. The goal of this study was to evaluate the anti‐tumour efficacy of interleukin‐7 (IL‐7) combining cisplatin against NSCLC. MATERIALS AND METHODS: Cell proliferation was analysed using CCK‐8 assay, EdU proliferation assay and colony‐forming assay. Cell apoptosis was evaluated using HOECHST 33342 assay and flow cytometry. The protein expression levels were analysed by Western blot. The blocking antibody against the IL‐7 receptor and the inhibitors of STAT5 and JAK3 were used to investigate the pathway involved. A xenograft model was established to assess the anti‐tumour efficacy of IL‐7 combining cisplatin in vivo. RESULTS: Here we found IL‐7R was increased in A549/DDP cells compared with A549 cells. The block of IL‐7R reversed the inhibitory effects of IL‐7 combined with cisplatin and decreased the numbers of apoptosis cells induced by treatment of IL‐7 combined with cisplatin. The JAK3 inhibitor and STAT5 inhibitor were used to identify the pathway involved. The results showed that JAK3/STAT5 pathway was involved in enhancing role of cisplatin sensitivity of NSCLC cells by IL‐7. In vivo, cisplatin significantly inhibited tumour growth and IL‐7 combined with cisplatin achieved the best therapeutic effect. CONCLUSION: Together, IL‐7 promoted the sensitivity of NSCLC cells to cisplatin via IL‐7R‐JAK3/STAT5 signalling pathway.