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

Abstract 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.