本文選題：NEDD　切入點(diǎn)：NSCLC　出處：《第三軍醫(yī)大學(xué)學(xué)報(bào)》2017年15期

【摘要】：目的探討NEDD4(neural precursor cell expressed developmentally downregulated protein 4)在非小細(xì)胞肺癌(non-small cell lung cancer,NSCLC)繼發(fā)厄洛替尼耐藥中的作用。方法以HCC827細(xì)胞及耐厄洛替尼的HCC827(HCC827/ER)細(xì)胞為工具,CCK-8法檢測(cè)HCC827/ER細(xì)胞的耐藥指數(shù);實(shí)時(shí)熒光定量PCR(quantitative real-time,q PCR)及Western blot檢測(cè)厄洛替尼處理48 h后,NEDD4 mRNA和蛋白在兩種細(xì)胞中的表達(dá)及PI3K/AKT信號(hào)通路活化情況。NEDD4小干擾RNA(si NEDD4)轉(zhuǎn)染HCC827/ER細(xì)胞,比較處理前后HCC827/ER細(xì)胞的厄洛替尼IC50變化以及PI3K/AKT信號(hào)通路活化情況。裸鼠成瘤實(shí)驗(yàn)在活體水平上進(jìn)一步驗(yàn)證NEDD4在NSCLC繼發(fā)厄洛替尼耐藥中的作用。結(jié)果HCC827/ER細(xì)胞的耐藥指數(shù)為(118.23±23.77);HCC827/ER細(xì)胞NEDD4 mRNA和蛋白以及PI3K/AKT信號(hào)通路活化水平均高于HCC827細(xì)胞;HCC827/ER細(xì)胞成功轉(zhuǎn)染si NEDD4后,轉(zhuǎn)染組的PI3K/AKT信號(hào)通路活化水平降低,且厄洛替尼IC50值明顯低于對(duì)照組(P0.05)。裸鼠成瘤實(shí)驗(yàn)中轉(zhuǎn)染組腫瘤對(duì)厄洛替尼的敏感性明顯增加,與陰性對(duì)照組比較,藥物處理組腫瘤生長(zhǎng)受到明顯的抑制。結(jié)論NEDD4通過激活PI3K/AKT信號(hào)通路促進(jìn)NSCLC繼發(fā)厄洛替尼耐藥。
[Abstract]:Objective to investigate the role of NEDD4(neural precursor cell expressed developmentally downregulated protein 4 in the development of erlotinib resistance secondary to non-small cell lung cancer in non-small cell lung cancer.Methods the drug resistance index of HCC827/ER cells was measured by CCK-8 method using HCC827 cells and HCC827- HCC827 / ER-ERcells of erlotinib as a tool.Real-time PCR(quantitative real-time PCR and Western blot were used to detect the expression of Neddd 4 mRNA and protein in two kinds of cells and the activation of PI3K/AKT signaling pathway. NEDD4 small interfering RNA(si NEDD4 was transfected into HCC827/ER cells after 48 h of erlotinib treatment.The changes of erlotinib IC50 and the activation of PI3K/AKT signaling pathway in HCC827/ER cells were compared before and after treatment.Tumorigenesis in nude mice further demonstrated the role of NEDD4 in erlotinib resistance secondary to NSCLC in vivo.Results the drug resistance index of HCC827/ER cells was 118.23 鹵23.77% HCC827 / ER cells. The activation levels of NEDD4 mRNA, protein and PI3K/AKT signaling pathway in ER cells were higher than those in HCC827 cells after successful transfection of HCC827 cell line HCC827 / ER cells. The activation level of PI3K/AKT signaling pathway in transfection group was lower than that in HCC827 cell line.The IC50 value of erlotinib was significantly lower than that of control group (P 0.05).The sensitivity of the transfected group to erlotinib was significantly increased in nude mice. Compared with the negative control group, the tumor growth of the drug treated group was significantly inhibited.Conclusion NEDD4 promotes erlotinib resistance secondary to NSCLC by activating PI3K/AKT signaling pathway.
【作者單位】： 第三軍醫(yī)大學(xué)新橋醫(yī)院全軍腫瘤研究所;
【基金】：國(guó)家自然科學(xué)基金面上項(xiàng)目(81672841) 重慶市科委重點(diǎn)攻關(guān)課題(2011AB5032)~~
【分類號(hào)】：R979.1

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