IL-25 promotes cisplatin resistance of lung cancer cells by activating NF-kappa B signaling pathway to increase of major vault protein
IL-25 promotes cisplatin resistance of lung cancer cells by activating NF-kappa B signaling pathway to increase of major vault protein
复制标题
IL-25通过激活NF-κB信号通路增加主要穹窿蛋白促进肺癌细胞顺铂耐药
DOI：
10.1002/cam4.2213
复制
发表时间：
2019
期刊：
影响因子：
4
通讯作者：
Wang Haidong
中科院分区：
文献类型：
--
作者：
Shen Weiming;Qiu Yang;Li Jingyao;Wu Chao;Liu Zhihui;Zhang Xiaorong;Hu Xiaohong;Liao Yi;Wang Haidong
IL-25作为一种炎症因子，在多种肿瘤中均有研究，但在肿瘤化疗耐药中的研究报道较少。主要穹窿蛋白（MVP）作为肺多药耐药相关基因，与肺癌的多药耐药相关。然而，肺癌细胞中IL-25和MVP之间的关系尚未研究。在本研究中，我们发现IL-25和MVP在顺铂耐药肺腺癌细胞系（A549/CDDP）中均表达升高。IL-25沉默导致MVP表达下调，并降低A549/CDDP细胞的顺铂耐受性。过表达IL-25可增加MVP的表达，提高A549细胞对顺铂的耐受性。另外，我们发现细胞外IL-25可以刺激MVP的表达，激活NF-κB信号通路。此外，动物模型也证实了IL-25降低了异种移植物对化疗的敏感性。综上所述，我们认为IL-25的上调诱导MVP表达有助于肺癌细胞的化疗抗性。我们的研究结果表明，干扰IL-25的表达可能是临床逆转化疗耐药性的潜在治疗策略。
As an inflammatory factor, IL‐25 has been studied in variouscancers, but it is rarely reported in cancer chemotherapy resistance. Major vault protein (MVP), as a gene associated with lung multidrug resistance, is associated with multiple chemotherapy resistances of lung cancer. However, the relationship between IL‐25 and MVP in lung cancer cells has not been studied. In this study, we found that both IL‐25 and MVP were elevated expressed in cisplatin‐resistant lung adenocarcinoma cell line (A549/CDDP). Silencing of IL‐25 resulted in down‐regulation of MVP expression and reduced cisplatin tolerance of A549/CDDP cells. Overexpression of IL‐25 resulted in increase of MVP expression and the cisplatin tolerance in A549 cells. In addition, we found that the extracellular IL‐25 could stimulate the expression of MVP and activate the NF‐κB signaling pathway. Further, animal models also confirmed that IL‐25 reduced the sensitivity of xenografts to chemotherapy. Taken together, we believe that the up‐regulation of IL‐25 induces MVP expression contributing to chemotherapy resistances of lung cancer cells. Our findings suggest that interference the expression of IL‐25 might be potential treatment strategies for the clinical reversing the chemotherapy resistance.