IL-13 Contributes to Drug Resistance of NK/T-Cell Lymphoma Cells by Regulating ABCC4.
IL-13 Contributes to Drug Resistance of NK/T-Cell Lymphoma Cells by Regulating ABCC4.
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IL-13 通过调节 ABCC4 促进 NK/T 细胞淋巴瘤细胞的耐药性。
DOI：
10.1155/2018/2606834
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发表时间：
2018
影响因子：
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通讯作者：
Zhang Mingzhi
中科院分区：
文献类型：
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作者：
Ni Mingli;Qin Beibei;Xie Ling;Zhang Xudong;Yang Jiezhi;Lv Hongqiong;Yang Mingyue;Zhang Mingzhi
背景结外自然杀伤/T(NK/T)细胞淋巴瘤，鼻型(ENKTL)，是一种罕见的T细胞淋巴瘤亚型，具有侵袭性的临床行为，对化疗相对耐药。然而，目前对ENKTL多药耐药的分子发病机制的研究相对较少。本研究旨在探讨IL-13和ABCC4在NK/T细胞淋巴瘤多药耐药中的生物学作用及其可能机制。方法采用酶联免疫吸附试验和免疫组织化学方法检测NK/T细胞淋巴瘤患者血清IL-13和ABCC4的表达水平。用免疫印迹法检测ABCC4在细胞中的表达。构建Lenti-sh-ABCC4病毒，在YTS细胞中击倒ABCC4。采用CCK-8比色法和流式细胞仪检测IL-13和ABCC4对细胞增殖和凋亡的影响。采用CCK-8法检测IL-13和ABCC4对YTS细胞对阿霉素(ADM)敏感性的影响。观察到NK/T细胞淋巴瘤患者血清IL-13和ABCC4表达水平升高。此外，与正常NK细胞相比，NK/T细胞淋巴瘤YTS细胞中ABCC4蛋白的表达也增加。有趣的是，IL-13促进了YTS细胞ABCC4的表达。IL-13促进YTS细胞增殖，抑制细胞凋亡，并逆转ABCC4基因敲除的促增殖和抑制细胞凋亡的作用。此外，IL-13还通过促进ABCC4的表达增强了YTS细胞对ADM的化疗耐药性。结论IL-13通过调节ABCC4的表达抑制了NK/T细胞淋巴瘤细胞对ADM的化疗敏感性，从而可能有效地改善耐药NK/T细胞淋巴瘤的治疗方案。
BackgroundExtranodal 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.MethodsELISA 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.ConclusionOur 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.