IL-13 Contributes to Drug Resistance of NK/T-Cell Lymphoma Cells by Regulating ABCC4.

Abstract

Background Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL), represents a rare subtype of T-cell lymphomas with aggressive clinical behavior and is relatively resistant to chemotherapy. However, there is relatively poor understanding of molecular pathogenesis of multidrug resistance in ENKTL. Here, we aimed to explore the biological roles and potential mechanism of IL-13 and ABCC4 in multidrug resistance of NK/T-cell lymphoma. Methods ELISA analysis was used to determine the level of serum IL-13 and immunohistochemical analysis was applied to detect the ABCC4 expression level in patients with human NK/T-cell lymphoma. Western blot assay was employed to measure the expression of ABCC4 in cells. Lenti-sh-ABCC4 viruses were constructed to knock down ABCC4 in YTS cells. CCK-8 assay and flow cytometric analysis were performed to detect the effects of IL-13 and ABCC4 on cell proliferation and apoptosis. CCK-8 assay was conducted to detect the effect of IL-13 and ABCC4 on cell sensitivity to adriamycin (ADM) in YTS cells. Results Levels of serum IL-13 and ABCC4 expression were observed to be upregulated in patients with human NK/T-cell lymphoma. Moreover, ABCC4 protein expression was also increased in NK/T-cell lymphoma YTS cells compared to the normal NK cells. Interestingly, IL-13 promoted ABCC4 expression in YTS cells. IL-13 promoted proliferation and suppressed apoptosis of YTS cells and reversed the effects of ABCC4 knockdown on promotive proliferation and inhibitory apoptosis. In addition, IL-13 enhanced YTS cell chemotherapy resistance to ADM by promoting ABCC4 expression. Conclusion Our findings concluded that IL-13 inhibited chemotherapy sensitivity of NK/T-cell lymphoma cells by regulating ABCC4, disrupting which may effectively improve the therapy protocols against resistant NK/T-cell lymphoma.