| 于雪姣,卫红军,张 芳,周 磊,黄维清.TNF-α对非小细胞肺癌中NF-κB/PXR信号通路和去SUMO化修饰的调控作用[J].,2020,(17):3221-3226 |
| TNF-α对非小细胞肺癌中NF-κB/PXR信号通路和去SUMO化修饰的调控作用 |
| Regulation of TNF-α on NF-κB/PXR Signaling Pathway and deSUMOylation Modulation in Non-small Cell Lung Cancer |
| 投稿时间：2020-03-20 修订日期：2020-04-17 |
| DOI：10.13241/j.cnki.pmb.2020.17.005 |
| 中文关键词: 非小细胞肺癌 TNF-α NF-κB PXR 去SUMO化 |
| 英文关键词: NSCLC TNF-α NF-κB PXR de-SUMOylation |
| 基金项目:山东省自然科学基金项目（ZR2016HM28）；青岛市医疗卫生重点学科建设项目（青卫科教字（2017）9号） |
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| 中文摘要: |
| 摘要 目的：研究肿瘤坏死因子α（tumor necrosis factor-alpha, TNF-α）在非小细胞肺癌(non-small cell lung cancer, NSCLC)中对NF-κB/PXR信号通路和去SUMO化（small ubiquitin-like modifier，SUMO）修饰的调控作用。方法：培养人正常肺上皮细胞系BEAS-2B和人非小细胞肺癌细胞系A549，在两种细胞系中加入人重组肿瘤坏死因子α(recombinant human tumor necrosis factor-alpha, rhTNF-α)，采用实时荧光定量PCR(qRT-PCR)方法检测核转录因子-κB (nuclear transcription factor-κB, NF-κB)、孕烷X受体（Pregnane X receptor, PXR）和多药耐药基因-1(multidrug resistance-1, MDR-1)以及包括SENP1、SENP2和SENP3在内的SUMO特异性蛋白酶(SUMO-specific proteases, SENPs)的mRNA水平的变化；采用细胞免疫组织化学染色的方法验证NF-κB、PXR和SENP1在蛋白水平的变化；采用Western blot方法检测磷酸化NF-κB的表达改变。结果：基础状态下，A549细胞系与BEAS-2B细胞系中NF-κB表达水平差异无统计学意义(P=0.745)；加入TNF-α诱导后，A549细胞系和BEAS-2B细胞系中NF-κB的mRNA和蛋白水平以及磷酸化NF-κB表达水平升高，A549细胞系中的NF-κB及磷酸化NF-κB表达水平均明显高于BEAS-2B细胞系(P<0.05)。基础状态下，A549细胞系中PXR、MDR-1及SENP1的表达明显高于BEAS-2B细胞系，SENP2及SENP3的表达明显低于BEAS-2B细胞系(P<0.05)；TNF-α诱导后，A549细胞系PXR、MDR-1、SENP1、SENP2和SENP3的表达均降低，但BEAS-2B细胞系中以上指标表达均升高(P<0.05)。结论：炎症因子TNF-α可以诱导NSCLC细胞系中NF-κB表达上调，PXR、MDR-1、SENP1、SENP2和SENP3的表达下调，提示TNF-α可能通过NF-κB/PXR炎症通路参与肿瘤的发生过程，并且，去SUMO化修饰可能参与TNF-α对NF-κB/PXR通路的调控作用。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the regulation of TNF-α (tumor necrosis factor-alpha) on NF-κB/PXR signaling pathway and deSUMOylation modulation in non-small cell lung cancer. Methods: Human normal lung epithelial BEAS-2B cell line and human non-small cell lung cancer A549 cell line were used to investigate the changes in mRNA of NF-κB (nuclear transcription factor-κB), PXR (Pregnane X receptor), MDR-1 (multidrug resistance-1) and deSUMOylation enzymes including SENP1, SENP2, and SENP3 in recombinant human TNF-α (rhTNF-α)-induced NSCLC A549 and BEAS-2B cell line by quantitative RT-PCR (qRT-PCR). Cellular immunochemical staining was used to verify the changes in protein levels of NF-κB, PXR and SENP1. Changes of phosphorylated NF-κB were detected by Western blot. Results: The baseline expression of NF-κB mRNA was similar in both A549 cell line and control(P=0.745). Increased expression of NF-κB in mRNA and protein levels as well as phosphorylated NF-κB after TNF-α treatment was found in A549 cell line and normal control. However, the expression in A549 cells was significantly higher than BEAS-2B cells (P<0.05). The baseline expression of PXR, MDR-1 and SENP1 is higher in A549 cells, but the expression of SENP2 and SENP3 was much lower compared to BEAS-2B cells (P<0.05). The TNF-α treatment decreased the expression of PXR, MDR-1, SENP1, SENP2 and SENP3 in A549 cells, but increased the expression in BEAS-2B cells (P<0.05). Conclusion: TNF-α is involved in the contribution of NF-κB/PXR signaling pathway to carcinogenesis in NSCLC cell line. In addition, de-SUMOylation may play a role in the regulation of TNF-α on NF-κB / PXR pathway. |
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