Antitumor activity of adenoviral vector containing T42 and 4xT42 peptide gene through inducing apoptosis of tumor cells and suppressing angiogenesis

Zhang,Xiong; Qi,Dong‑Dong; Zhang,Ting‑Ting; Chen,Qing‑Xin; Wang,Guang‑Zhi; Sui,Guang‑Yu; Hao,Xue‑Wei; Sun,Shouli; Song,Xue; Chen,Ying‑Li

doi:10.3892/mmr.2014.2910

Antitumor activity of adenoviral vector containing T42 and 4xT42 peptide gene through inducing apoptosis of tumor cells and suppressing angiogenesis

Authors:
- Xiong Zhang
- Dong‑Dong Qi
- Ting‑Ting Zhang
- Qing‑Xin Chen
- Guang‑Zhi Wang
- Guang‑Yu Sui
- Xue‑Wei Hao
- Shouli Sun
- Xue Song
- Ying‑Li Chen
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Affiliations: Department of Psychiatry, Hulunbeier Mental Health Center, Yakeshi, Inner Mongolia 022150, P.R. China, Clinical Laboratory, Hulunbeier Mental Health Center, Yakeshi, Inner Mongolia 022150, P.R. China, Department of Urinary Surgery, General Hospital of Daqing Oil Field, Daqing, Heilongjiang 163000, P.R. China, Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China, Department of Pathology, The Fifth Affiliated Hospital, Harbin Medical University, Daqing, Heilongjiang 163319, P.R. China, Clinical Laboratory, Chinese Medicine Hospital of Daqing, Daqing, Heilongjiang 163319, P.R. China, Department of Immunology, College of Medical Laboratory Science and Technology, Harbin Medical University‑Daqing, Daqing, Heilongjiang 163319, P.R. China
Published online on: November 10, 2014 https://doi.org/10.3892/mmr.2014.2910
Pages: 2083-2091

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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.

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