文章摘要
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*
Inducing effects of TNF-αon NF-κB/PXR signaling pathway and deSUMOylation modulation in non-small cell lung cancer *
投稿时间:2020-03-30  修订日期:2020-04-07
DOI:
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:青岛市医疗卫生重点学科建设项目(青卫科教字(2017)9号)。
作者单位E-mail
于雪姣 青岛大学基础医学院病理学教研室 山东 青岛 中国 517597789@qq.com 
卫红军 青岛市市立医院病理科 山东 青岛 中国  
张芳 青岛市市立医院病理科 山东 青岛 中国  
周磊 青岛市市立医院病理科 山东 青岛 中国  
黄维清 青岛市市立医院病理科 山东 青岛 中国 huangweiqing_40@163.com 
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中文摘要:
      目的:研究TNF-α在非小细胞肺癌(NSCLC)中对NF-κB/PXR信号通路和去SUMO化修饰的调控作用。方法:培养人正常肺上皮BEAS-2B细胞系和人非小细胞肺癌A549细胞系,在两种细胞系加入TNF-α,采用实时荧光定量PCR(qRT-PCR)方法,检测NF-κB、PXR和MDR-1以及包括SENP1、SENP2和SENP3在内的去SUMO化酶的mRNA水平的变化。并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。结果:在基础状态下,A549细胞与BEAS-2B细胞中NF-κB表达水平没有差异(P=0.745);TNF-α诱导后,NF-κB在A549细胞和BEAS-2B细胞中表达都升高,但在A549细胞中的表达水平明显高于BEAS-2B细胞(P<0.05)。基础状态下,A549细胞中PXR、MDR-1及SENP1的表达明显高于BEAS-2B细胞,SENP2及SENP3的表达明显低于BEAS-2B细胞;TNF-α诱导后,PXR、MDR-1、SENP1、SENP2和SENP3的表达在A549细胞中降低,在BEAS-2B细胞中表达均升高(P<0.05)。结论:TNF-α可能通过激活NF-κB及相关NF-κB/ PXR炎症通路在非小细胞肺癌肿瘤发生及耐药过程中发挥重要作用,去SUMO化修饰与炎症因子参与肿瘤发生过程密切相关。
英文摘要:
      ABSTRACT Objective: To explore inducing effects of TNF-α 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 cultured, to investigate changes in mRNA alterations of NF-κB, PXR, MDR-1 and de-SUMOylation enzymes including SENP1, SENP2, and SENP3 in TNF-α induced inflammatory response in 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.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 after TNF-α treatment was found in A549 cell line and normal control,however the expression in A549 cells was significantly higer 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. 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). Conclusions: The current results indicated the activation of NF-κB and related NF-κB/PXR signaling pathway by TNF-α may play important roles in carcinogenesis and drug resistance of NSCLC, as well as de-SUMOylation was proposed to involve in modulation of inflammation in NSCLC carcinogenesis.
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