Abstract |
Gene transfer using different viral vectors has demonstrated different antitumor effects in suicide gene therapy. In the present study, in order to optimize the efficacy of replication-defective adenoviral and lentiviral vectors for gene therapy, RT-PCR was used to evaluate the expression of Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK) in the Bcap37 human breast cancer cell line, dThd was used to determine the activity of Dm-dNK, cell cytotoxicity was evaluated by MTT assay and cell proliferation was assessed using a hemocytometer. Moreover, apoptosis induction was evaluated by the Annexin V- FITC-labeled FACS method. Furthermore, BALB/C nude mice bearing tumors were treated with Dm-dNK mediated with the pyrimidine nucleoside analog, brivudine [BVDU, (E)-5-(2-bromovinyl)-2'- deoxyuridine]. Our results indicated that the gene expression of Dm-dNK transfected by adenoviral and lentiviral vectors may be detected and that its long-term activity may be retained. Both vectors containing the Dm-dNK gene revealed high cytotoxicity and sensitized cell apoptosis from the BVDU prodrug. In tumor models, lentivirus-mediated gene therapy significantly inhibited the growth of tumors compared with adenovirus-mediated gene therapy. Although adenovirus- and lentivirus-transduced Dm-dNK reveal strong treatment efficacy in vitro, the latter has great potential due to the long-term expression of the therapeutic gene in vivo.
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Authors | Nianqu Zhang, Xiaoshen Dong, Yiqun Sun, Xiaopeng Cai, Caiwei Zheng, Anning He, Ke Xu, Xinyu Zheng |
Journal | Oncology reports
(Oncol Rep)
Vol. 29
Issue 3
Pg. 960-6
(Mar 2013)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 23254508
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Drosophila Proteins
- PHB2 protein, human
- Phb2 protein, mouse
- Prodrugs
- Prohibitins
- brivudine
- Phosphotransferases (Alcohol Group Acceptor)
- deoxyribonucleoside kinases
- Bromodeoxyuridine
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Topics |
- Adenoviridae
(genetics)
- Animals
- Antineoplastic Agents
(metabolism, pharmacology)
- Apoptosis
- Breast Neoplasms
(pathology, therapy)
- Bromodeoxyuridine
(analogs & derivatives, metabolism, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
- Cell Survival
(drug effects)
- Combined Modality Therapy
- Drosophila Proteins
(biosynthesis, genetics)
- Female
- Gene Expression
- Genetic Therapy
- Genetic Vectors
- HEK293 Cells
- Humans
- Lentivirus
(genetics)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Phosphotransferases (Alcohol Group Acceptor)
(biosynthesis, genetics)
- Prodrugs
(metabolism, pharmacology)
- Prohibitins
- Tumor Burden
(drug effects)
- Xenograft Model Antitumor Assays
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