登录    
  
首页 > 期刊论文 > 论文摘要
GRIM-19基因对肺腺癌耐药细胞株A549/DDP药物敏感性及相关基因表达的影响
         
Effects of GRIM-19 on chemotherapeutic sensitivity of cisplatin-resistant human lung cancer cell A549/DDP and the expressions of related genes

摘    要
目的:本研究旨在探讨干扰素/维甲酸诱导凋亡相关基因19(gene-associated with retinoid-interferon-induced mortality19,GRIM-19)对人肺腺癌耐药细胞株A549/DDP化疗药物敏感度及相关基因表达的影响。方法:采用脂质体法将重组质粒PIRES-Puro2-GRIM-19-Myc和空载体PIRES-Puro2-Myc分别转染顺铂(cisplatin,DDP)耐药的人肺腺癌细胞株A549/DDP。蛋白免疫印迹法检测亲本A549、耐药A549/DDP、转染GRIM-19基因的A549/DDP及转染空载体的A549/DDP细胞中GRIM-19蛋白的表达。MTT法检测稳定转染GRIM-19基因后A549/DDP细胞对多种化疗药物敏感度的改变。实时荧光定量-PCR(real-time fluorescence quantitative-PCR,RFQ-PCR)法检测GRIM-19、信号转导子与转录激活子3(signal transducers and activators of transcription 3,STAT3)、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)和P-糖蛋白(P-glycoprotein,P-gp)mRNA在稳定转染GRIM-19基因后A549/DDP细胞中的表达情况。结果:蛋白质印迹法检测结果显示,A549/DDP细胞转染GRIM-19基因后GRIM-19蛋白的表达上调;A549/DDP细胞较亲本A549细胞对DDP的耐药指数为16.86±1.32;A549/DDP细胞转染GRIM-19基因后,较转染空载体组A549/DDP细胞耐药性降低,耐药逆转倍数为3.70±0.91。转染GRIM-19基因后,A549/DDP细胞中STAT3、P-gp和VEGFmRNA表达均下调。结论:GRIM-19能增强DDP耐药细胞A549/DDP对化疗药物的敏感度,这可能与下调STAT3、VEGF和P-gp的表达具有相关性,GRIM-19可能成为逆转A549/DDP细胞耐药性的一条有效途径。
标    签   非小细胞肺   干扰素/维甲酸诱导凋亡相关基因-19   药物耐受性   转染   A549/DDP细胞   Carcinoma   non-small cell lung   Gene associated with retinoid-interferon-induced mortality 19   Drug tolerance   Transfection   A549/DDP cells  
 
Abstract
Objective: To investigate the effects of gene-associated with retinoid-interferon-induced mortality 19(GRIM-19) on chemotherapeutic sensitivity of cisplatin(DDP)-resistant human lung caner cell A549/DDP and the expressions of related genes. Methods: The recombinant plasmid PIRES-Puro2-GRIM-19- Myc and the empty vector PIRES-Puro2-Myc were transfected into A549/DDP cells by liposome transfection reagent, respectively. The expression levels of GRIM-19 protein in the A459 parental cells, A459/DDP cells, A549/DDP cells transfected with GRIM-19 gene and A549/DDP cells transfected with an empty vector were detected by Western blotting. The changes of chemotherapeutic sensitivities to multi-drugs in A549/DDP cells stably transfected with GRIM-19 gene were detected by MTT assay. The expression levels of GRIM-19, signal transducers and activators of transcription 3(STAT3), vascular endothelial growth factor(VEGF) and P-glycoprotein(P-gp) mRNAs in the A549/DDP cells stably transfected with GRIM-19 gene were examined by real-time fluorescence quantitative-PCR(RFQ-PCR). Results: The Western blotting result showed that the expression level of GRIM-19 protein was increased in the A549/DDP cells after transfection with GRIM-19 gene. The resistance index of A549/DDP cells was 16.86±1.32 folds higher than that of the A549 parental cells. The resistance index of the A549/DDP cells after transfection with GRIM-19 gene was decreased by 3.70±0.91 folds as compared with that of the A549/DDP cells transfected with an empty vector. The expression levels of STAT3, VEGF and P-gp mRNAs in the A549/DDP cells transfected with GRIM-19 gene were decreased. Conclusion: GRIM-19 can increase the chemotherapeutic sensitivity of A549/DDP cells. This effect may be associated with the down-regulations of STAT3, VEGF and P-gp. GRIM-19 may become a potential therapeutic agent to reverse drug-resistance in A549/DDP cells.

中图分类号 R734.2   DOI 10.3781/j.issn.1000-7431.2012.02.003

 
  购买该论文  中国光学期刊网论文下载说明
      


所属栏目 基础研究

基金项目 安徽省科技计划资助项目(编号:10021303028)

收稿日期 2011/9/13

修改稿日期 2012/1/17

网络出版日期

作者单位点击查看


引用该论文: WU Dao-rong,WANG Tong,JIANG Zi-feng,LIU Rong-yu. Effects of GRIM-19 on chemotherapeutic sensitivity of cisplatin-resistant human lung cancer cell A549/DDP and the expressions of related genes[J]. Tumor, 2012, 32(2): 92~98
武道荣,王同,江子丰,刘荣玉. GRIM-19基因对肺腺癌耐药细胞株A549/DDP药物敏感性及相关基因表达的影响[J]. 肿瘤, 2012, 32(2): 92~98


论文评价
共有人对该论文发表了看法,其中:
人认为该论文很差
人认为该论文较差
人认为该论文一般
人认为该论文较好
人认为该论文很好
分享论文
分享到新浪微博 分享到腾讯微博 分享到人人网 分享到 Google Reader 分享到百度搜藏分享到Twitter

参考文献
【1】ANGELL J E, LINDNER D J, SHAPIRO P S, et al. Identification of GRIM-19, a novel cell deathregulatory gene induced by the interferonbeta and retinoic acid combination, using a genetic approach[J]. J Biol Chem, 2000, 275(43):33416-33426.
 
【2】KALVAKOLANU D V. The GRIMs:a new interface between cell death regulation and interferon/retinoid induced growth suppression[J]. Cytokine Growth Factor Rev, 2004, 15(2-3):169-194.
 
【3】ALCHANATI I, NALLAR S C,SUN P, et al. A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas[J]. Oncogene, 2006, 25(54):7138-7147.
 
【4】WANG T, YAN X B, ZHAO J J, et al. Gene associated with retinoid-interferon-induced mortality-19 suppresses growth of lung adenocarcinoma tumor in vitro and in vivo[J]. Lung Cancer, 2011, 72(3):287-293.
 
【5】赵继京, 叶静, 黄燕, 等. 肺癌中GRIM-19 mRNA的表达及临床意义[J]. 安徽医科大学学报, 2008,43(6)595-598.
 
【6】ZHOU Y, LI M, WEI Y, et al. Down-regulation of GRIM-19 expression is associated with hyper activation of STAT3-induced gene expression and tumor growth in human cervical cancers[J]. J Interferon Cytokine Res, 2009, 29(10):695-703.
 
【7】BOURGUIGNON L Y, PEYROLLIER K, XIA W, et al. Hyaluronan-CD44 interaction activates stem cell marker, nanog, Stat-3-mediated MDR 1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells[J]. J Biol Chem, 2008, 283(25):17635-17651.
 
【8】ZHANG X, LIU P, ZHANG B, et al. Role of STAT3 decoy oligodeoxy nucleotides on cell invasion and chemosensitivity in human epithelial ovarian cancer cells[J]. Cancer Genet Cytogenet, 2010,197(1):46-53.
 
【9】HUANG Y, YANG M, YANG H, et al. Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line[J]. Exp Cell Res, 2010, 316(13):2061-2070.
 
【10】BUETTNER R, MORA L B, JOVE R, et al. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention[J]. Clin Cancer Res, 2002, 8(4):945-54.
 
【11】LIANG X, HUANG Y. Intracellular free calcium concentration and cisplatin resistance in human lung adenocarcinoma A549 cells[J]. Biosci Rep, 2000, 20(3):129-38.
 
【12】FEARNLEY I M, CARROLL J, SHANNON R J, et al. GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex Ⅰ)[J]. J Biol Chem, 2001, 276(42):38345-38348.
 
【13】MURRAY J, ZHANG B, TAYLOR S W, et al. The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification[J]. J Biol Chem, 2003, 278(16):13619-13622.
 
【14】ZHANG J, YANG J, ROY S K, et al. The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3[J]. Proc Natl Acad Sci U S A, 2003, 100(16):9342-9347.
 
【15】COMERFORD K M, WALLACE T J, KARHAUSEN J, et al. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene[J]. Cancer Res, 2002, 62(12):3387-3394.
 
【16】REUEFLI A A, SMYTH M J, JOHNSTONE R W, et al. HMBA induces activation of a caspaseindependent cell death pathway to overcome p-glycoprotein-mediated multidrug resistance[J]. Blood, 2000, 95(7):2378-2385.
 
【17】李维方, 张光霁, 朱诚, 等. VEGF反义寡核苷酸对C6胶质瘤细胞VEGF表达和内皮细胞生长的抑制作用[J]. 肿瘤, 2001, 21(5):331-333.
 
【18】WEI D, LE X, ZHENG L, et al. Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis[J]. Oncogene, 2003, 22(3):319-329.
 
【19】OSMAK M, NIKSIC D, A, et al. Drug resisitant tumor cells have increased levels of tumor markers for invasion and metastasis[J]. Anticancer Res, 1999, 19(4B):3193-3197.
 
相关信息
   标题 相关频次
 人肺腺癌细胞株A549和A549/DDP的比较蛋白质组学研究
 6
 SLC22A18基因对人胶质瘤U251细胞化疗药物敏感性的影响
 4
 H2O2氧化刺激对紫杉醇耐药和敏感肺癌细胞的不同影响
 4
 Luffin-β靶向融合免疫毒素的构建、表达及对非小细胞肺癌的抑制作用
 4
 单药培美曲塞二线治疗晚期非小细胞肺癌的疗效观察
 4
 胆固醇酯转运蛋白对人宫颈癌HeLa细胞辐射增敏性的影响
 4
 非小细胞肺癌组织中血管内皮生长因子表达与树突状细胞分布的关系
 4
 高海拔地区老年非小细胞肺癌患者接受全电视胸腔镜下肺叶切除的安全性和预后分析
 4
 化疗序贯厄洛替尼治疗二线厄洛替尼耐药晚期非小细胞肺癌的临床疗效和安全性
 4
 抗原致敏及白细胞介素27基因修饰的树突状细胞诱导抗食管癌免疫的体外研究
 4
 上皮-间质转化和胰岛素样生长因子Ⅰ型受体在非小细胞肺癌EGFR-TKIs获得性耐药中的作用
 4
 重组人血管内皮抑制素联合含铂方案治疗晚期非小细胞肺癌的临床观察
 4
 多靶点受体酪氨酸激酶抑制剂联合化疗治疗晚期非小细胞肺癌的Meta分析
 3
 非小细胞肺癌CD44v6表达的免疫组化研究
 3
 突变的MTX耐药基因对骨髓造血干细胞的保护作用
 3
 B7-1基因转染骨肉瘤细胞诱导抗骨肉瘤主动免疫的实验研究
 2
 c-myc反义寡核苷酸对表达FHIT基因的结肠癌细胞增殖及凋亡作用的影响
 2
 HepaCAM基因转染对肾癌细胞侵袭活性的影响
 2
 ING4基因表达对乳腺癌细胞生长抑制作用的研究
 2
 15-羟基前列腺素脱氢酶基因转染对人胃癌细胞生长和迁移的影响
 2
 2009年恶性肿瘤临床治疗新进展
 2
 34例卵巢透明细胞癌临床分析
 2
 Autotaxin在人卵巢癌基因及蛋白水平表达的研究及意义
 2
 B7-1 基因转染后对小鼠体内的免疫增强作用
 2
 bcl-Xs基因转移与羟基喜树碱对卵巢癌细胞生长抑制的协同效应
 2
 C-myc蛋白在睾丸肿瘤中的表达及意义
 2
 cRGD-氧化铁纳米粒的构建及应用于核磁共振成像诊断中的动物研究
 2
 EB病毒的BARF1基因在人支气管上皮细胞恶性转化和肿瘤形成中的作用
 2
 FRNK抑制人乳腺癌细胞体外增殖及机制研究
 2
 GRIM-19表达对子宫颈癌HeLa细胞增殖的影响
 2

  热点专题


关于我们  |   联系我们  |   广告投放  |   《肿瘤》杂志社版权所有 《肿瘤》杂志社   © 中国 上海 2014.3
沪ICP备15036656号-2