IL-25 promotes cisplatin resistance of lung cancer cells by activating NF-κB signaling pathway to increase of major vault protein.

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.
(© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)