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H2O2氧化刺激对紫杉醇耐药和敏感肺癌细胞的不同影响
         
The different reactions of chemo-resistant and chemo-sensitive lung adenocarcinoma cells to redox stimulation of H2O2

摘    要
目的:探讨腺癌株A549及紫杉醇(paclitaxel)耐药株A549/Taxol 对于H2O2氧化刺激的不反应性及可能的作用机制。 方法:用不浓度的H2O2处理A549及A549/Taxol 后,采用计数试剂盒-8(cell counting kit-8,CCK-8)检测存活率,并计算半数抑制浓度(half inhibitory concentration,IC50)值;采用荧光探针氯甲基-2',7'-二氯二氢荧光素二乙酯[5-(and-6)-chloromethyl-2',7'-dichlorofluoresceindiacetate acctyl ester,CM-H2DCFDA]染色法检测内活性氧(reactive oxygen species,ROS)水平;甲基罗丹明甲酯(tetramethylrhodamine methyl ester perchlorate,TMRM)染色法检测线粒体膜电位水平;AnnexinⅤ-FITC/PI双染法检测凋亡率;实时荧光定量-PCR法检测内超氧化歧化酶1(superoxide dismutase 1,SOD1)、SOD2、过氧化氢酶(catalase,CAT)、γ-谷氨酰半胱氨酸链接酶(glutamate-cysteine ligase,GCL)、谷胱甘肽合成酶(glutathione synthetase,GSS)谷胱甘肽还原酶(glutathione reductase,GSR)mRNA表达的变化。 结果:耐药株A549/Taxol 对H2O2的IC50值高于亲本株A549;采用低毒浓度H2O2(50100 μmol/L)作用2 h后,A549/Taxol 中的ROS水平增高幅度显著低于A549,A549/Taxol 的线粒体膜电位保持相对稳定而A549显著增高,且A549/Taxol 的凋亡发生率显著低于A549。A549/Taxol 中抗氧化系统相关基因SOD1、SOD2、CAT、GCL、GSSGSR mRNA的表达量高于A549;在H2O2作用后,A549中上述基因表达量显著增高,而A549/Taxol 中仅GSR mRNA表达上调。 结论:紫杉醇耐药对氧化刺激的耐受能力显著高于敏感株,其机制可能与耐药自身氧化-还原平衡系统的适应性变化有关。
标    签   非小细胞肺   紫杉醇   抗药性   肿瘤   氧化性应激   Carcinoma   non-small cell lung   Paclitaxel   Drug resistance   neoplasm   Oxidative stress  
 
Abstract
Objective:To investigate the different reactions of paclitaxel-resistant subline A549/Taxoland its parental sensitive cell line A549 to redox stimulation of H2O2 and to explore its possible mechanism. Methods:To investigate the different reactions of paclitaxel-resistant subline A549/Taxoland its parental sensitive cell line A549 to redox stimulation of H2O2 and to explore its possible mechanism. Results:The IC50value of A549/Taxol cells was significantly lower than that of A549 cells after redox stimulation of H2O2.After short-term 2 h treatment with low dose of H2O2 (50 and 100 μmol/L), the increasing degree of ROSlevel in A549 cells was significantly higher than that in A549/Taxol cells, the mitochondrial membrane potential of A549/Taxol cells remained relatively stable while that of A549 cells rised significantly, and the apoptosis rate of A549/Taxol cells was significantly lower than that of A549 cells. The mRNA expression levels of anti-redox-related genes including SOD1, SOD2, CAT, GCL, GSS and GSR were higher in A549/Taxol cells than those in A549 cells. The expression levels of these genes were increased significantly in A549 cells, but in A549/Taxol cells, only the expression level of GSR mRNA was increased slightly afterredox stimulation of H2O2. Conclusion:The resistant ability to redox stimulation for paclitaxel-resistantA549/Taxol cells was significantly stronger than of parental sensitive A549 cells. This mechanism may be associated with the adaptive balancing of oxidation-reduction system in A549/Taxol cells.

中图分类号 R734.2   DOI 10.3781/j.issn.1000-7431.2013.05.006

 
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所属栏目 基础研究

基金项目 国家自然科学基金资助项目(编号:30970842)

收稿日期 2013/1/12

修改稿日期 2013/3/12

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引用该论文: LI Rui,LIU Jian-jun,HUANG Gang. The different reactions of chemo-resistant and chemo-sensitive lung adenocarcinoma cells to redox stimulation of H2O2[J]. Tumor, 2013, 33(5): 415~421
李蕊,刘建军,黄钢. H2O2氧化刺激对紫杉醇耐药和敏感肺癌细胞的不同影响[J]. 肿瘤, 2013, 33(5): 415~421


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