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硒结合蛋白1通过抑制超氧化物歧化酶增强奥沙利铂的细胞毒作用 被引量：2

Selenium-Binding Protein 1 Enhances Oxaliplatin-Induced Cytotoxicity Through Inhibiting Superoxide Dismutase
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摘要 目的:探讨人硒结合蛋白1(SBP1)在结直肠癌DLD-1细胞中的表达水平对超氧化物歧化酶(SOD)的影响及其引起的DLD-1细胞对奥沙利铂的敏感性变化,揭示SBP1的部分抗肿瘤作用机制。方法:MTS法检测不同浓度奥沙利铂处理SBP1siRNA或SOD1siRNA转染细胞后的细胞存活率,CuZn/Mn-SOD活性检测试剂盒检测SBP1siRNA转染对DLD-1细胞SOD酶活性的影响;实时荧光定量PCR检测下调SBP1后,SOD1和SOD2mRNA水平的变化;Western blot法检测下调SBP1或SOD1后DLD-1细胞内SBP1、SOD1及SOD2蛋白水平的变化;超氧化物阴离子荧光探针DHE染色法检测抗肿瘤药物引起的细胞内超氧化物阴离子的水平。结果:下调SBP1后,奥沙利铂对DLD-1细胞的毒性作用[半数毒性浓度IC50为(36.7±1.6)μmol/L]相比对照组[IC50为(17.5±0.8)μmol/L]明显减小(P<0.05);同时下调SBP1和SOD1后,奥沙利铂对DLD-1细胞的毒性作用[IC50为(16.8±1.0)μmol/L]相比对照组[IC50为(17.3±1.2)μmol/L]无明显变化(P>0.05);下调SBP1分别在转录水平、蛋白水平及酶活性水平上调了SOD,并减少了由奥沙利铂引起的DLD-1细胞内产生的超氧阴离子。结论:下调SBP1能上调SOD的水平,进而减小了奥沙利铂对DLD-1细胞的毒性作用,故SBP1能通过抑制SOD增强奥沙利铂对DLD-1细胞的毒性作用。 Objective：To investigate the role of selenium-binding protein 1（SBP1）in oxaliplatin-mediated cytotoxicity and the role of SBP1 in the regulation of superoxide dismutase（SOD）in human colorectal cancer DLD-1cells,and to reveal the anti-tumor mechanisms of SBP1.Methods：MTS assay was used to detect the cell viability in DLD-1cells transfected with SBP1 or control siRNA following the treatment of different concentrations of oxaliplatin.CuZn/MnSOD activity assay kit was used to detect the enzymatic activity of SOD in DLD-1cells.Real-time PCR was employed to evaluate the mRNA levels of SOD1 and SOD2in DLD-1cells following the SBP1 or control siR-NA transfection.Western blot assay was employed to detect the protein levels of SBP1,SOD1 and SOD2.DHE staining was employed to determine the amount of superoxide anion caused by oxaliplatin.Results：DLD-1cells with SBP1 siRNA transfection were more sensitive to oxaliplatin than DLD-1with control siRNA transfection.Furthermore,SBP1 knockdown increased the mRNA and protein levels of SOD1 and SOD2,and also elevated the enzymatic activity of SOD.Down-regulation of SOD1 in DLD-1（siSBP1）cells abolished the effects of SBP1 knockdown on oxaliplatin-induced cytotoxicity and superoxide anion.Conclusion：Selenium-binding protein 1enhanced the cytotoxicity of oxaliplatin through inhibiting superoxide dismutase（SOD）in cancer cells.
作者 胡芬 王钰雷 熊斌
机构地区 武汉大学中南医院肿瘤科/湖北省肿瘤生物学行为重点实验室/湖北省肿瘤医学临床研究中心
出处 《武汉大学学报（医学版）》 CAS 2015年第3期363-368,共6页 Medical Journal of Wuhan University
基金 国家863计划资助项目子课题(编号:2012AA02A506)
关键词 DLD-1细胞 硒结合蛋白-1 超氧化物歧化酶 DLD-1Cells Selenium-Binding Protein 1 Superoxide Dismutase
分类号 R735.3 [医药卫生—肿瘤]
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参考文献13

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二级参考文献16

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共引文献4

同被引文献24

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武汉大学学报（医学版）
2015年 第3期

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