|本期目录/Table of Contents|

[1]孙 杰,刘 淦,李因茵,等.MLN4924 对索拉非尼耐药肝细胞癌细胞中neddylation 修饰的抑制作用[J].传染病信息,2019,03:215-219.
 SUN Jie,LIU Gan,LI Yin-yin,et al.MLN4924 inhibits neddylation modification in sorafinib-resistant HCC cells[J].Infectious Disease Information,2019,03:215-219.
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MLN4924 对索拉非尼耐药肝细胞癌细胞中neddylation 修饰的抑制作用(PDF)

《传染病信息》[ISSN:1007-8134/CN:11-3886/R]

期数:
2019年03期
页码:
215-219
栏目:
论 著
出版日期:
2019-07-12

文章信息/Info

Title:
MLN4924 inhibits neddylation modification in sorafinib-resistant HCC cells
文章编号:
   1007-8134(2019)03-0215-05    
作者:
孙 杰刘 淦李因茵陆荫英
100853北京,解放军医学院(孙杰、陆荫英);100039北京,中国人民解放军总医院第五医学中心肝脏肿瘤诊疗与研究中心(孙杰、刘淦、李因茵、陆荫英)
Author(s):
SUN Jie LIU Gan LI Yin-yin LU Yin-ying*
Medical School of Chinese PLA, Beijing 100853, China Comprehensive Liver Cancer Center, the Fifth Medical Center of Chinese Military General Hospital, Beijing 100039, China
关键词:
Neddylation修饰索拉非尼MLN4924肝细胞癌
Keywords:
neddylation modification sorafinib MLN4924 hepatocellular carcinoma
分类号:
R392.11;R735.7    
DOI:
10.3969/j.issn.1007-8134.2019.03.005
文献标识码:
A
摘要:
目的 索拉非尼是美国 FDA于 2007年批准的治疗肝细胞癌( hepatocellular carcinoma, HCC)的一线小分子抑制剂。然而,其在 HCC患者中的反应率不高。本研究旨在进一步了解索拉非尼在 HCC治疗中的作用机理,为 HCC靶向治疗方法的优化提供理论基础。方法 使用蛋白印迹方法检测经索拉非尼治疗前后 HCC细胞中与 neddylation修饰相关蛋白的表达水平。通过 CCK实验检测 HCC细胞的增殖速率。结果 本研究发现索拉非尼能激活 neddylation修饰相关的蛋白的表达。神经前体细胞表达的发育性下调蛋白 8 (neuronal precursor cell-expressed developmentally down-regulated protein 8, NEDD8)激活酶抑制剂 MLN4924通过抑制 neddylation修饰来抑制索拉非尼耐药细胞的增殖。结论 索拉非尼能引起 neddylation通路的活化。泛素激活酶 NAE抑制剂可以进一步抑制对索拉非尼耐药的 HCC细胞的增殖。  
Abstract:
Objective Sorafinib is the first-line micromolecule inhibitor which has been approved by the U.S. Food and Drug Administration (FDA) for hepatocellular carcinoma (HCC) treatment in 2007. However, the overall response rate is not satisfactory. This paper aims to reveal the mechanism of sorafinib therapy in HCC. Methods Neddylation modification-related protein expression inHCC cell lines with or without sorafinib treatment was detected. HCC cell proliferation rate was measured by CCK experiment. Results In this study, we found neddylation modification related protein expression was activated with sorafinib treatment in HCC cell lines. MLN4924, an inhibitor of neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8)-activating enzyme (NAE), could suppress the proliferation of sorafinib-resistant cells by inhibiting neddylation modification. Conclusions Sorafinib treatment induces activation of neddylation pathway. NEDD8-activating enzyme NAE inhibitor can further inhibit the proliferation of sorafinib-resistantHCC cells.      

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备注/Memo

备注/Memo:
[基金项目] 北京市自然科学基金(7172207)8, NEDD8)
[作者单位] 100853北京,解放军医学院(孙杰、陆荫英);100039北京,中国人民解放军总医院第五医学中心肝脏肿瘤诊疗与研究中心(孙杰、刘淦、李因茵、陆荫英)
[通信作者] 陆荫英,E-mail: luyinying1973@163.com
更新日期/Last Update: 2019-07-12