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A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines
Xie, Min1,3; Niu, Ji-Hong1,3; Chang, Yan1,3; Qian, Qi-Jun2; Wu, Hong-Ping2; Li, Lin-Fang2; Zhang, Yao1,3; Li, Jin-Lan1,3; Huang, Xiao-Jun1,3; Ruan, Guo-Rui1,3
关键词PDCD5 Gene therapy Conditionally replicating adenoviruses Leukemia Nude mice
刊名APOPTOSIS
2009-09-01
DOI10.1007/s10495-009-0373-3
14期:9页:1086-1094
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]EXPRESSION PROFILES ; HEPATOCELLULAR-CARCINOMA ; MYELOGENOUS LEUKEMIA ; CANCER-TREATMENT ; VIRAL THERAPY ; TUMOR-CELLS ; IN-VIVO ; HTERT ; APOPTOSIS ; METASTASIS
英文摘要

PDCD5 (programmed cell death 5) accelerates apoptosis of certain tumor cells and the replication-defective Ad-PDCD5 may be a promising agent for enhancing chemosensitivity. In this study, a triple-regulated conditionally replicating adenoviruses (CRAd) carrying PDCD5 gene expression cassette, SG611-PDCD5, was engineered. In SG611-PDCD5, the E1a gene with a deletion of 24 nucleotides within CR2 region is controlled under the human telomerase reverse transcriptase (hTERT) promoter, the E1b gene expression is directed by the hypoxia response element (HRE), whereas the PDCD5 gene is controlled by the cytomegalovirus promoter. The tumor-selective replication of this virus and its antitumor efficacy were characterized in several leukemic cell lines in vitro and in xenograft models of human leukemic cell line in nude mice. It was found by RQ-RT-PCR assay that SG611-PDCD5 expressed PDCD5 efficiently in leukemic cells. In K562 tumor xenograft models, SG611-PDCD5 displayed a tumor killing capacity. At a dose of 1 x 10(9) plaque-forming units, SG611-PDCD5 alone could completely inhibit the tumor growth and more effective than replication-defective Ad-PDCD5. Histopathologic examination revealed that SG611-PDCD5 administration resulted in leukemic cell apoptosis. We concluded that the triple-regulated SG611-PDCD5, as a more potent and safer antitumor therapeutic, could provide a new strategy for leukemia biotherapy.

语种英语
WOS记录号WOS:000268743500006
项目编号30670894 ; 2006AA02A405
资助机构National Natural Science Foundation of China ; National High Technology Research and Development Program of China (863 Program)
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60146
专题北京大学第二临床医学院_血液科
北京大学第一临床医学院_骨科
作者单位1.Peking Univ, Inst Hematol, Beijing 100044, Peoples R China
2.Peking Univ, Peoples Hosp Hematol, Beijing 100044, Peoples R China
3.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Viral & Gene Therapy, Shanghai 200438, Peoples R China
推荐引用方式
GB/T 7714
Xie, Min,Niu, Ji-Hong,Chang, Yan,et al. A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines[J]. APOPTOSIS,2009,14(9):1086-1094.
APA Xie, Min.,Niu, Ji-Hong.,Chang, Yan.,Qian, Qi-Jun.,Wu, Hong-Ping.,...&Ruan, Guo-Rui.(2009).A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines.APOPTOSIS,14(9),1086-1094.
MLA Xie, Min,et al."A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines".APOPTOSIS 14.9(2009):1086-1094.
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