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基于代谢组学的多西他赛调控肺癌细胞代谢重编程研究 被引量:5
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作者 孙海超 朴海龙 +2 位作者 齐欢 颜敏 刘宏旭 《中国肺癌杂志》 CAS CSCD 北大核心 2019年第4期208-215,共8页
背景与目的多西他赛是一种临床常用的抗肿瘤药物,是晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的一线用药。然而,多西他赛抗NSCLC作用的分子机制尚不明确。研究表明肿瘤细胞的代谢重编程在肿瘤发生发展过程中发挥重要作用。... 背景与目的多西他赛是一种临床常用的抗肿瘤药物,是晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的一线用药。然而,多西他赛抗NSCLC作用的分子机制尚不明确。研究表明肿瘤细胞的代谢重编程在肿瘤发生发展过程中发挥重要作用。本研究旨在通过结合代谢组学分析及生物学手段来探讨多西他赛所影响的NSCLC细胞代谢通路。方法首先,通过CCK-8实验分析多西他赛对NSCLC细胞活力的影响,筛选合适药物浓度。接下来,通过基于气相色谱质谱联用(gas chromatography-mass spectrometry, GC-MS)的代谢组学技术分析多西他赛处理和未处理的A549和H1299细胞。并通过统计学计算得到处理组和未处理组间的差异代谢物。最后,通过蛋白质免疫印迹分析(Western blot)多西他赛对其所调控的相关代谢途径中关键酶蛋白质表达水平的影响。结果多西他赛可时间依赖和浓度依赖地抑制A549和H1299细胞活力。随着多西他赛处理时间延长,凋亡敏感蛋白质多聚二磷酸腺苷核糖聚合酶[Poly(ADP-)Polymerase, PARP]逐渐被激活裂解形成P89片段。代谢组学分析发现,药物处理后的A549和H1299细胞内,8种代谢物均发生显著变化,主要集中于三羧酸(tricarboxylic acid, TCA)循环代谢通路。同时,药物处理后,TCA循环关键调控酶异柠檬酸脱氢酶蛋白质表达水平显著下降。结论多西他赛诱导NSCLC增殖抑制及凋亡的效应可能与下调异柠檬酸脱氢酶,进而抑制三羧酸循环代谢途径有关。 展开更多
关键词 多西他赛 肺肿瘤 气相色谱质谱联用 代谢组学 三羧酸循环
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UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis 被引量:2
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作者 Lei FANG Huan QI +5 位作者 Peng WANG Shiqing WANG Tianjiao LI Tian XIA hailong piao Chundong GU 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2022年第10期863-875,共13页
Up-frameshift 1(UPF1),as the most critical factor in nonsense-mediated messenger RNA(mRNA)decay(NMD),regulates tumor-associated molecular pathways in many cancers.However,the role of UPF1 in lung adenocarcinoma(LUAD)a... Up-frameshift 1(UPF1),as the most critical factor in nonsense-mediated messenger RNA(mRNA)decay(NMD),regulates tumor-associated molecular pathways in many cancers.However,the role of UPF1 in lung adenocarcinoma(LUAD)amino acid metabolism remains largely unknown.In this study,we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics.We further confirmed that UPF1 knockdown inhibited activating transcription factor 4(ATF4)and Ser51 phosphorylation of eukaryotic translation initiation factor 2α(eIF2α),the core proteins in amino acid metabolism reprogramming.In addition,UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells,which depends on the function of ATF4.Clinically,UPF1 mRNA expression is abnormal in LUAD tissues,and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival(OS)in LUAD patients.Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD. 展开更多
关键词 Up-frameshift 1(UPF1) Activating transcription factor 4(ATF4) Amino acid metabolism Lung adenocarcinoma
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Rapid screening of SARS-CoV-2 inhibitors via ratiometric fluorescence of RBD–ACE2 complexes in living cells by competitive binding 被引量:1
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作者 Lu Miao Wei Zhou +14 位作者 Chunyu Yan Yuebin Zhang Qinglong Qiao Xuelian Zhou Yingzhu Chen Guangying Wang Zhendong Guo Jun Liu hailong piao Xia Pan Mengxue Yan Weijie Zhao Guohui Li Yueqing Li Zhaochao Xu 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2022年第9期3739-3742,共4页
To the Editor:The current coronavirus disease-19(COVID-19)pandemic spurs the development of antiviral drugs for SARS-CoV-2,as the number of patients with viral infections continues to rise globally in the context of w... To the Editor:The current coronavirus disease-19(COVID-19)pandemic spurs the development of antiviral drugs for SARS-CoV-2,as the number of patients with viral infections continues to rise globally in the context of widespread vaccination.Targeting the interaction between the receptor binding domain(RBD)of SARS-CoV-2 spike protein and the host cell ACE2 is a promising therapeutic strategy to effectively inhibit viral entry. 展开更多
关键词 SARS-CoV-2 RBD–ACE2 interaction Inhibitors screening Live-cell imaging
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