A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines
A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines
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携带PDCD5基因的新型三重调控溶瘤腺病毒对常见人类白血病细胞系发挥有效的抗肿瘤功效
作者：
PDCD 5（programmedcelldeath 5）可促进某些肿瘤细胞的凋亡，而复制缺陷型Ad-PDCD 5可能是一种有前途的化疗增敏剂。本研究设计了一种携带PDCD 5基因表达盒的三重调控条件复制型腺病毒SG 611-PDCD 5。在SG 611-PDCD 5中，E1 a基因在CR2区域内缺失24个核苷酸，由人端粒酶逆转录酶（hTERT）启动子控制，E1 b基因的表达由缺氧反应元件（HRE）指导，而PDCD 5基因由巨细胞病毒启动子控制。该病毒的肿瘤选择性复制和其抗肿瘤疗效的特点，在几个白血病细胞系在体外和人白血病细胞系在裸鼠移植瘤模型。RT-PCR检测发现SG 611-PDCD 5在白血病细胞中高效表达PDCD 5。在K562肿瘤异种移植模型中，SG 611-PDCD 5显示出肿瘤杀伤能力。在1 × 109空斑形成单位的剂量下，SG 611-PDCD 5可完全抑制肿瘤的生长，且抑制效果优于复制缺陷型Ad-PDCD 5。组织学检查显示SG 611-PDCD 5给药导致白血病细胞凋亡。结论：SG 611-PDCD 5作为一种更有效、更安全的抗肿瘤药物，有望为白血病的生物治疗提供新的策略。
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 × 109plaque-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.
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影响因子：
2.1
作者：
H. Miyake;I. Hara;S. Hara;S. Arakawa;S. Kamidono
通讯作者：
H. Miyake;I. Hara;S. Hara;S. Arakawa;S. Kamidono
影响因子：
3.1
作者：
LaBarre, DD;Lowy, RJ
通讯作者：
Lowy, RJ
DOI：
10.1073/pnas.0408260101
发表时间：
2004-12-28
影响因子：
11.1
作者：
Zucchi, I;Mento, E;Dulbecco, R
通讯作者：
Dulbecco, R
影响因子：
12.8
作者：
H. Huh;J. Huh;E. Yoo;C. Seong;Miae Lee;K. Hong;W. Chung
通讯作者：
H. Huh;J. Huh;E. Yoo;C. Seong;Miae Lee;K. Hong;W. Chung
DOI：
10.1016/j.ymthe.2005.12.011
发表时间：
2006-05
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
C. Su;Lin-hui Peng;J. Sham;Xing-hua Wang;Qi Zhang;D. Chua;Chen Liu;Z. Cui;Hui-bin Xue;Hongping Wu;Qin Yang;Bai-he Zhang;Xinyuan Liu;Mengchao Wu;Q. Qian
通讯作者：
C. Su;Lin-hui Peng;J. Sham;Xing-hua Wang;Qi Zhang;D. Chua;Chen Liu;Z. Cui;Hui-bin Xue;Hongping Wu;Qin Yang;Bai-he Zhang;Xinyuan Liu;Mengchao Wu;Q. Qian