IL-7-Mediated IL-7R-JAK3/STAT5 signalling pathway contributes to chemotherapeutic sensitivity in non-small-cell lung cancer
IL-7-Mediated IL-7R-JAK3/STAT5 signalling pathway contributes to chemotherapeutic sensitivity in non-small-cell lung cancer
复制标题
IL-7介导的IL-7R-JAK3/STAT5信号通路有助于非小细胞肺癌的化疗敏感性
DOI：
10.1111/cpr.12699
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发表时间：
2019-11-01
影响因子：
8.5
通讯作者：
Ke, Bin
中科院分区：
文献类型：
--
作者：
Shi, Lin;Xu, Zhaozhong;Ke, Bin
目的非小细胞肺癌（NSCLC）化疗耐药是其治疗面临的主要挑战。免疫疗法和化学疗法的组合已经显示出对癌症的希望。本研究的目的是评估白细胞介素-7（IL-7）联合顺铂对非小细胞肺癌的抗肿瘤疗效。材料与方法采用CCK-8法、EdU法和集落形成法检测细胞增殖。采用HOECHST 33342法和流式细胞术检测细胞凋亡。蛋白质表达水平通过Western blot分析。使用针对IL-7受体的阻断抗体以及STAT 5和JAK 3的抑制剂来研究所涉及的通路。建立异种移植模型以评估IL-7联合顺铂的体内抗肿瘤功效。结果A549/DDP细胞IL-7 R表达较A549细胞明显增高。阻断IL-7 R可逆转IL-7联合顺铂的抑制作用，减少IL-7联合顺铂诱导的凋亡细胞数。JAK 3抑制剂和STAT 5抑制剂用于鉴定所涉及的通路。结果表明JAK 3/STAT 5通路参与了IL-7增强NSCLC细胞对顺铂敏感性的作用。在体内，顺铂显着抑制肿瘤生长和IL-7联合顺铂达到最佳的治疗效果。结论IL-7通过IL-7 R-JAK 3/STAT 5信号通路促进NSCLC细胞对顺铂的敏感性。
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.