期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

人MUC4启动子驱动的HSV-TK重组腺病毒靶向杀伤SGC-7901胃癌细胞的实验研究 被引量：1

Targeting cytotoxic effect of recombinant adenovirus carrying HSV-TK driven by MUC4 promoter on SGC-7901 gastric cancer cells
原文传递
导出
摘要 目的:构建人粘蛋白(MUC4)启动子驱动下的单纯疱疹胸苷激酶基因(HSV-TK)重组腺病毒,研究其对SGC-7901胃癌细胞的靶向杀伤作用。方法:克隆MUC4启动子区625bp活性序列,构建重组荧光素酶报告基因载体pGL3-MUC4,检测其在SGC-7901胃癌细胞及NIH3T3成纤维细胞中的转录活性。以AdEasyTM腺病毒系统为载体,构建MUC4启动子驱动下的HSV-TK重组腺病毒rAdeno-MUC4-TK,感染SGC-7901及NIH3T3,经更昔洛韦(GCV)处理,MTT法检测细胞活力,TUNEL法检测细胞凋亡。结果:成功扩增出大小为625bp的MUC4启动子序列。pGL3-MUC4在SGC-7901细胞中具有强转录活性,转录活性高于强启动子SV40 6.6倍,而NIH3T3成纤维细胞系中几乎无转录活性。构建重组腺病毒rAdeno-MUC4-TK,MTT法和TUNEL检测结果显示,其与GCV联合能够诱导SGC-7901细胞凋亡,产生靶向细胞毒作用。结论:人MUC4启动子驱动下的HSV-TK重组腺病毒联合GCV对SGC-7901胃癌细胞具有靶向杀伤作用,MUC4启动子可以作为胃癌靶向基因治疗的工具。 OBJECTIVE： To construct the recombinant adenovirus carrying herpes simplex virus thymidine kinase （HSV-TK） driven by human mucin 4 （MUC4） promoter and analyze its selective cytotoxic effect in vitro on human gas tric cancer cell line SGC 7901 combined with ganciclovir （GCV）. METHODS： The fragment of MUC4 promoter from hu man genome DNA and construct pGL3-MUC4 recombinant luciferase report vector were coloned and its transcriptional ac- tivities in SGC-7901 and NIH3T3 cell lines was analyzed. The recombinant adenovirus carrying HSV-TK driven by hu man MUC4 promoter （rAdeno-MUC4-TK） based on AdEasyTM adenoviral system was constructed and the selective cy- totoxie effect of the recombinant adenovirus on SGC-7901 cells combined with prodrug GCV was analyzed by MTT and TUNEL assays. RESULTS： Totally 625 bp MUC4 promoter fragment was coloned by PCR. pGI.3--MUC4 showed high tran- scriptional activitiy in SGC 7901 cell 6.6 time stronger than SV40 strong promoter but little in NIH3T3 fibroblast cell. rAdeno- MUC4-TK combined with C^V could evidently inhibit the proliferation of SGC-7901 cells and induce cell apoptosis, but showed low activity in NIH3T3 fibroblast cell. CONCLUSION： Adenoviral-mediated suicide gene therapy controlled by MUC4 promoter can induce specific cytotoxic effect on SCA2-7901 gastric cancer cells,suggesting MUC4 promoter can be serve as a useful tool for transcriptional targeting of gastric cancer gene therapy.
作者 陈衍 韩晟 刘文超
机构地区 第四军医大学西京医院肿瘤内科 第四军医大学口腔医院信息科
出处 《中华肿瘤防治杂志》 CAS 北大核心 2012年第1期10-14,共5页 Chinese Journal of Cancer Prevention and Treatment
基金 国家自然科学基金(81001180) 陕西省自然科学基金(2010JM4005)
关键词 粘蛋白 启动区/遗传学 转录 遗传 基因疗法 腺病毒 人 mucin promoter regions/genetics transcription, genetic gene therapy adenoviruses, human
分类号 R735.2 [医药卫生—肿瘤]
  • 相关文献

参考文献4

二级参考文献37

  • 1师英强,宗祥云,王亚农,莫善兢.结直肠高级别上皮内瘤变的临床意义及外科治疗(附83例报告)[J].中国癌症杂志,2004,14(5):406-409. 被引量：24
  • 2吴云林.早期胃癌的临床筛查及治疗[J].外科理论与实践,2005,10(5):401-403. 被引量：29
  • 3刘磊,李梅,罗锋.晚期胃癌的化疗新进展[J].华西医学,2007,22(2):430-431. 被引量：5
  • 4吴云林,吴巍,郭滟,蔚青,江凤翔,胡伟国,燕敏,朱正纲.胃黏膜高级别上皮内瘤变的内镜识别与手术病理的结果[J].上海交通大学学报（医学版）,2007,27(5):552-554. 被引量：43
  • 5Tomizawa M,Yu L,Wada A,et al.A promoter region of the midkine gene that is frequently expressed in human HCC can activate a suicide gene as effectively as the alpha-fetoprotein promoter[J].Br J Cancer,2003,89(6):1086-1090.
  • 6Shalev M,Miles BJ,Thompson TC,et al.Suicide gene therapy for prostate cancer using a replication-deficient adenovirus containing the herpesvirus thymidine kinase gene[J].World J Urol,2000,18(2):125-129.
  • 7Vassaux G,Martin-Duque P.Use of suicide genes for cancer gene therapy:study of the different approaches[J].Expert Opin Biol Ther,2004,4(4):519-530.
  • 8Vassaux G,Martin-Duque P.Use of suicide genes for cancer gene therapy:study of the different approaches[J].Expert Opin Biol Ther,2004,4(4):519-530.
  • 9Niculescu-Duvaz I,Springer CJ.Introduction to the background,principles,and state of the art in suicide gene therapy[J].Mol Biotechnol,2005,30(1):71-88.
  • 10Hall EJ.The bystander effect[J].Health Phys,2003,85(1):31-35.

共引文献38

同被引文献20

  • 1De Zio Dv Ferraro E,D' Amelio Mv et al.Fafl is expressed during neurodevelopment and is involved in Apafl-dependent caspase-3 activation in proneural cells[J].Cell Mol Life Sci,2008,65(11):1780-1790.
  • 2Zhang LvZhou F,Li Yv et al.Fas-associated factor 1 is a scaffold protein that promotes beta-transducin repeat-containing protein(beta-TrCP)-mediated beta-catenin ubiquitination and degradation[J].J Biol Chem,2012,287(36):30701-30710.
  • 3Altomare DA,Menges CW,Pei 1,et al.Activated TNF-alpha/NF-kappaB signaling via down-regulation of Fas-associated factor 1 in asbestos-induced mesotheliomas from Arf knockout mice [J].Proc Natl Acad Sci USA,2009,106(9):3420-3425.
  • 4Gryko M,Guzinska-Ustymowicz Kv Pryczynicz Av et al.Correlation between Fas and Fast proteins expression in normal gastric mucosa and gastric cancer[J].Folia Histochem Cytobiol,2011,49(1):142-147.
  • 5Park MY,Ryu SW,Kim KD,et al.Fas-associated factor-1 mediates chemotherapeutic-induced apoptosis via death effector filament formation[J].Int J Cancer,2005,115(3):412-418.
  • 6Lee JJ.Park JK,leong J,et al.Complex of las-associated factor 1(FAF1) with valosin-containing protein(VCP)-npI4-ufd1 and polyubiquitinated proteins promotes endoplasmic reticulum-asso-ciated degradation(ERAD)[J].J Biol Chem,2013,288(10):6998-7011.
  • 7Song J.Park JK,Lee II,et al.Structure and interaction of ubiquitin-associated domain of human Fas-associated factor 1 [J].Protein Sci,2009,18(11):2265-2276.
  • 8Bjorling-Poulsen M,Seitz G,Guerra B,et al.The pro-apoptotic FAS-associated factor 1 is specifically reduced in human gastric carcinomas[J].Int J Oncol,2003,23(4):1015-1023.
  • 9Liu AQ,Ge L Y,Ye XQ,et al.Reduced F AF1 expression and he-licobacter infection:correlations with clinicopathological features in gastric cancer [J].Gastroenterol Res Pract,2012,2012:153219.
  • 10Hyland PL,Lin SW,Hu N,et al.Genetic variants in fas signaling pathway genes and risk of gastric eancer[J].Int J Cancer,2013,134(4):822-831.

引证文献1

二级引证文献2

中华肿瘤防治杂志
2012年 第1期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部