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Antitumor activity of adenoviral vector containing T42 and 4xT42 peptide gene through inducing apoptosis of tumor cells and suppressing angiogenesis.
- Source :
-
Molecular medicine reports [Mol Med Rep] 2015 Mar; Vol. 11 (3), pp. 2083-91. Date of Electronic Publication: 2014 Nov 10. - Publication Year :
- 2015
-
Abstract
- The T42 peptide, generated from two active fragments of tumstatin, has been shown to have anti‑tumor activity. The adenoviral vector is the most frequently used vector in research and clinical trials for gene therapy. In the present study, the anti‑tumor activity of the T42 peptide and quadruple T42 (4xT42) peptide adenoviral vectors were elucidated for the first time, to the best of our knowledge. Human embryonic kidney 293 cells were infected with plasmid adenovirus (pAd)‑enhanced green fluorescent protein (EGFP)‑T42 or pAd‑EGFP‑4xT42 and the expression of the T42 and 4xT42 genes was confirmed by the identification of GFP expression and reverse transcription polymerase chain reaction experiments. The anti‑cancer effects of pAd‑EGFP‑T42 and pAd‑EGFP‑4xT42 on breast cancer cells in vivo and in vitro were subsequently investigated. The results indicated that the packaging of the recombinant adenoviruses with the viral titer was successful, following purification at 5x109 plaque forming units/ml. The results also revealed that the recombinant adenoviruses promoted apoptosis in MCF‑7 breast cancer cells and inhibited cancer growth. Through the analysis of caspase‑3, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein expression, it was demonstrated that the T42/4xT42 peptide may induce apoptosis via the mitochondrial pathway. In addition, mouse xenograft experiments confirmed that the T42 peptide inhibited tumor growth and reduced angiogenesis in vivo. In conclusion, the results of the present study indicated that the T42 and 4xT42 peptide genes, transfected by a recombinant adenovirus, may provide a potential novel strategy for the treatment of breast cancer.
- Subjects :
- Animals
Autoantigens chemistry
Cell Line, Tumor
Collagen Type IV chemistry
Disease Models, Animal
Female
Gene Expression
Genes, Reporter
Genetic Vectors administration & dosage
HEK293 Cells
Humans
MCF-7 Cells
Mice
Transfection
Xenograft Model Antitumor Assays
Adenoviridae genetics
Apoptosis genetics
Autoantigens genetics
Collagen Type IV genetics
Genetic Vectors genetics
Neovascularization, Pathologic genetics
Peptide Fragments genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1791-3004
- Volume :
- 11
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular medicine reports
- Publication Type :
- Academic Journal
- Accession number :
- 25384346
- Full Text :
- https://doi.org/10.3892/mmr.2014.2910