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A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines

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Abstract

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 × 109 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.

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Acknowledgments

This study was supported by the grant from National Natural Science Foundation of China (No.: 30670894) and supported in part by the grant from the National High Technology Research and Development Program of China (863 Program) (No.: 2006AA02A405).

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Authors and Affiliations

  1. Peking University People’s Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, 100044, Beijing, China

    Min Xie, Ji-Hong Niu, Yan Chang, Yao Zhang, Jin-Lan Li, Xiao-Jun Huang & Guo-Rui Ruan

  2. Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, 200438, Shanghai, China

    Qi-Jun Qian, Hong-Ping Wu & Lin-Fang Li

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  1. Min Xie
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  2. Ji-Hong Niu
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  3. Yan Chang
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  4. Qi-Jun Qian
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  5. Hong-Ping Wu
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  6. Lin-Fang Li
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  7. Yao Zhang
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  8. Jin-Lan Li
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  9. Xiao-Jun Huang
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  10. Guo-Rui Ruan
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Correspondence to Guo-Rui Ruan.

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Xie, M., Niu, JH., Chang, Y. et al. A novel triple-regulated oncolytic adenovirus carrying PDCD5 gene exerts potent antitumor efficacy on common human leukemic cell lines. Apoptosis 14, 1086–1094 (2009). https://doi.org/10.1007/s10495-009-0373-3

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  • DOI: https://doi.org/10.1007/s10495-009-0373-3

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