紫花牡荆素对脂多糖诱导的BEAS-2B细胞损伤和NF-κB-Keap1-Nrf2/ARE通路的影响

目的:探讨紫花牡荆素(CAS)对脂多糖诱导的人正常肺上皮细胞(BEAS-2B)损伤和NF-κB-Keap1-Nrf2/ARE通路的影响。方法:利用不同浓度的CAS预处理BEAS-2B细胞1 h、2 h、4 h,用1μg/ml脂多糖处理BEAS-2B细胞,构建细胞损伤模型,ELISA检测细胞上清炎症因子含量,筛选CAS最适作用浓度和时间;再将细胞分为正常组、模型组、Casticin组、ML385组、Casticin+ML385组、地塞米松组;流式细胞术检测细胞凋亡,ELISA检测细胞上清炎症因子的浓度,Western blot检测细胞NF-κB p65、p-NF-κB p65、Keap1、Nrf2以及细胞核中的Nrf2蛋白水平。结果:CAS最适作用条件为10μmol/L、2 h;与正常组相比,模型组的细胞凋亡率、炎症因子含量、p-NF-κB p65和Keap1蛋白表达水平显著升高(P<0.01),细胞和细胞核中Nrf2蛋白的表达水平显著降低(P<0.01);与模型组相比,Casticin组和地塞米松组的细胞凋亡率和炎症因子含量显著降低(P<0.01),Casticin组p-NF-κB p65和Keap1蛋白表达水平显著降低(P<0.01),细胞和细胞核中Nrf2蛋白的表达水平显著升高(P<0.01);与ML385组相比,Casticin+ML385组的细胞凋亡率,炎症因子含量,p-NF-κB p65和Keap1蛋白表达水平显著降低(P<0.01),细胞和细胞核中Nrf2蛋白的表达水平显著升高(P<0.01)。结论:CAS通过调节NF-κB-Keap1-Nrf2/ARE信号通路,抑制脂多糖诱导的细胞炎症。

自噬蛋白p62的促癌机制及与妇科恶性肿瘤关系的研究进展

代表性自噬相关蛋白p62具有参与细胞信号转导、细胞增殖、细胞凋亡、炎症、肿瘤发生和氧化应激反应等过程的多种功能。p62可介导Keap1-Nrf2、mTORC1、NF-κB等信号通路并导致细胞自噬紊乱,从而促进肿瘤的发生发展。组织中p62过表达可导致妇科恶性肿瘤的发生,如宫颈癌、卵巢癌、和子宫内膜癌等,且p62水平与肿瘤进展、肿瘤分级及患者生存率均具有相关性。p62及其上、下游分子有望成为预测妇科恶性肿瘤患者临床转归的标记物及治疗靶点。

Review the oncogenic mechanism of autophagy protein p62 and the relationship between p62 and gynecological malignant cancer

There are many fuctions with the representative autophagy associated protein p62,such as cell signal transduction,cell proliferation,apoptosis,inflammation,tumorigenesis and oxidative stress.p62 over express will lead to autophagy disorder by controlling keap1-Nrf2mTORC1,NF-κB signaling pathways,thus promoting the development of the tumor.The overexpression of p62 in tissues can lead to the occurrence of the gynecological malignant tumors,such as ceicival cancer,ovarian carcinoma and Endometrial carcinoma.And the level of p62 is correlated with the tumor progression,the tumor grade and the survival rates of patients.p62 and its upstream and downstream molecules are expected to be the markers and therapeutic targets for predicting the clinical outcome of the gynecological malignant cancer patients.