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溶瘤腺病毒SG7605-11R-P53对肝癌细胞的体外杀伤作用

Cytotoxicity effect of oncolytic adenovirus SG7605-11R-P53 on hepatocellular carcinoma cells in vitro
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摘要 目的：研究携带细胞穿膜肽11R和P53的溶瘤腺病毒SG7605-11R-P53对肝癌细胞的体外杀伤作用。方法：以本课题组前期实验构建的携细胞穿膜肽11R和P53的溶瘤腺病毒SG7605-11R-P53和不携11R的溶瘤腺病毒SG7605-P53感染肝癌细胞HepG2、SMMC-7721、Hep3B、Huh7和正常成纤维细胞株BJ,Western blotting检测感染后细胞P53和11R-P53的表达情况,TCID50法检测SG7605-11R-P53和SG7605-P53在肝癌细胞中的增殖能力,MTT法检测SG7605-11R-P53对肝癌细胞及正常细胞的杀伤作用。结果：SG7605-11R-P53和SG7605-P53能在肝癌细胞中高表达P53和11R-P53蛋白。SG7605-11R-P53可在HepG2、SMMC-7721、Hep3B和Huh7细胞中大量增殖,其增殖倍数是SG7605-P53的10100倍,但在正常BJ细胞内几乎不增殖。SG7605-11R-P53在MOI=0.1时对Hep3B细胞的杀伤率达90%,对于正常BJ细胞只有当MOI=50时才有很弱的抑制作用;SG7605-11R-P53对4种肝癌细胞杀伤作用的大小依次为Hep3B、HepG2、Huh7和SMMC-7721细胞。结论：携带细胞穿膜肽11R和P53的SG7605-11R-P53溶瘤腺病毒体外对4种肝癌细胞株均有较好的靶向杀伤作用,尤其对Hep3B细胞的杀伤作用最强。 Objective： To study the cytotoxicity of oncolytic adenovirus SG7605-11R-P53 containing cell-penetrating peptide（11R） on hepatocellular carcinoma cells Hep3B and Huh7 in vitro.Methods： Western blotting analysis was used to detect the expression levels of P53 and 11R-P53 in hepatocellular carcinoma cell lines HepG2,SMMC-7721,Hep3B and Huh7,and normal cell line BJ after SG7605-11R-P53 and SG7605-P53 infection.TCID50 assay was used to evaluate the replication ability of SG7605-11R-P53 and SG7605-P53 in hepatocellular carcinoma cell lines;the cytotoxicity of SG7605-11R-P53 on hepatocellular carcinoma cell lines and normal cell line was evaluated by MTT assay.Results： P53 and 11R-P53 proteins were highly expressed in both SG7605-11R-P53 and SG7605-P53 infected hepatocellular carcinoma cell lines.SG7605-11R-P53 replicated in HepG2,SMMC-7721,Hep3B and Huh7 cells but could hardly replicate in normal BJ cells,and SG7605-11R-P53 had a 10-100 times higher replication than SG7605-P53.When MOI=1,the cytotoxicity rate of SG7605-11R-P53 against Hep3B cells was 90%,and when MOI increased to 50,SG7605-11R-P53 only had a weak inhibitory effect against normal BJ cells.The cytotoxicity effect of SG7605-11R-P53 against Hep3B,HepG2,Huh7 and SMMC-7721 cells decreased gradually.Conclusion： Adenovirus SG7605-11R-P53 containing cell-penetrating peptide（11R） can efficiently kill the 4 hepatocellular carcinoma cell lines in vitro,with the strongest effect seen on Hep3B cells.This study lays a foundation for further investigating the effect of SG7605-11R-P53 against liver cancer in vivo
作者 于丽 陈艳 付玉华 范丽 刘辉 苏长青 钱其军
机构地区 浙江理工大学生命科学学院新元医药和生物技术研究所 第二军医大学东方肝胆外科医院基因与病毒治疗实验室
出处 《中国肿瘤生物治疗杂志》 CAS CSCD 北大核心 2011年第4期378-382,共5页 Chinese Journal of Cancer Biotherapy
基金 国家新药创制重大专项课题(No.2009ZX09102-235)~~
关键词 溶瘤腺病毒 细胞穿膜肽 11R P53 肝癌 基因-病毒治疗 oncolytic adenovirus cell-penetrating peptide 11R P53 hepatocellular carcinoma cell gene-viral therapy
分类号 R730.5 [医药卫生—肿瘤] R735.7 [医药卫生—肿瘤]
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参考文献19

  • 1Biederer C, Ries S, Brandts CH, et al. Replication-selective viruses for cancer therapy [J]. J Mol Med, 2002, 80(3) : 163-175.
  • 2Zhang Q, Chen G, Peng L, et al. Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus [J]. Clin Cancer Res, 2006, 12(21 ) : 6523-6527.
  • 3Zhang Y, Gu J, Zhao L, et al. Complete elimination of colorectal tumor xenograft by combined manganese superoxide dismutase with tumor necrosis factorr elated apoptosis-inducing ligand gene virotherapy [J]. Cancer Res, 2006, 66(8) : 4291-4310.
  • 4Liu XY, Qiu SB, Zou WG, et al. Effective gene-virotherapy for complete eradication of tumor mediated by the combination of hTRAIL (TNFSFIO) and plasminogen k5 [ J]. Mol Ther, 2005, 11(4) : 531-541.
  • 5Brosh R, Rotter V. When mutants gain new powers: News from the mutant p53 field [J]. Nat Rev Cancer, 2009, 9(10) : 701-713.
  • 6Ventura A, Kirsch DG, McLaughlin ME, et al. Restoration of p53 function leads to tumour regression in vivo [ J ]. Nature, 2007, 445(7128) : 661-665.
  • 7Wang X, Su C, Cao H, et al. A novel triple-regulated oncolytic adenovirus carrying p53 gene exerts potent antitumor efficacy on common human solid cancers [ J]. Mol Cancer Ther, 2008, 7 (6) : 1598-1603.
  • 8He X, Liu J, Yang C, et al. 5/35 fiber-modified conditionally replicative adenovirus armed with p53 shows increased tumor-suppressing capacity to breast cancer ceils [ J]. Hum Gene Ther, 2010, 22(3) : 283-292.
  • 9Takenobu T, Tomizawa K, Matsushita M, et al. Development of p53 protein transduction therapy using membrane-permeable peptides and the application to oral cancer ceils [ J]. Mol Cancer Ther, 2002, 1(12): 1043-1049.
  • 10Michiue H, Tomizawa K, Matsushita M, et al. Ubiquitination-resistant p53 protein transduction therapy facilitates anti-cancer effect on the growth of human malignant glioma ceils [ J ]. FEBS Lett, 2005, 579(18): 3965-3969.

二级参考文献19

  • 1Soussi T.p53 alterations in human cancer:more questions than answers[J].Oncogene,2007,26(15):2145-2156.
  • 2Tarasov V,Jung P,Verdoodt B,et al.Differential regulation of microRNAs by p53 revealed by massively parallel sequencing:miR-34a is a p53 target that induces apoptosis and G1-arrest[J].Cell Cycle,2007,6(13):1586-1593.
  • 3He L,He X,Lim L P,et al.A microRNA component of the p53 tumour suppressor network[J].Nature,2007,447:1130-1134.
  • 4Dubikovskaya E A,Thorne S H,Pillow T H,et al.Overcoming multidrug resistance of small-molecμLe therapeutics through conjugation with releasable octaarginine transporters[J].Proc Natl Acad Sci,2008,105(34):12128-12133.
  • 5Lowe S,Cepero W,Evan G.Intrinsic tumour suppression[J].Nature,2004,432:307-315.
  • 6Vousden K H,Lane D P.p53 in health and disease[J].Nature Rev Mol Cell Biol,2007,8:275-283.
  • 7Vogelstein B,Lane D,Levine A J.Surfing the p53 network[J].Nature,2000,408:307-310.
  • 8Tomasini R,Mak T W,Melino G.The impact of p53 and p73 on aneuploidy and cancer[J].Trends Cell Biol,2008,18(5):244-252.
  • 9Hiroshi I,Suzuki,Kaoru Yamagata,et al.Modulation of microRNA processing by p53[J].Nature,2009,460:529-533.
  • 10Mudhasani R,Zhu Z,Hutvagner G.et al.Loss of miRNA biogenesis induces p19Arf-p53 signaling and senescence in primary cells[J].Cell Biol,2008,181:1055-1063.
中国肿瘤生物治疗杂志
2011年 第4期

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