Abstract |
Vasostatin, a 180-amino acid fragment from the N-terminal domain of calreticulin, is a potent endogenous angiogenesis inhibitor, which can inhibit the growth of many kinds of experimental tumor. But a recent report that vasostatin can enhance the malignant behavior of neuroendocrine tumor reminds us to be cautious to develop it as an anti- tumor medicine. VAS cDNA was cloned into pAAV-2 expression vector; recombinant virus rAAV-VAS was generated by a three plasmids, helper free packaging method. MS1 mouse pancreatic endothelial cell and human colon tumor HCT-116 cell were infected with rAAV-VAS. Transgene expression was analyzed by Western blotting analysis; cell proliferation was determined by MTT assay. The therapeutic potential of rAAV-VAS was evaluated in subcutaneous HCT-116 xenograft mouse model. rAAV-VAS inhibited the proliferation of MS1 but not HCT-116 cell. HCT-116 cell infected with rAAV-VAS secreted VAS protein into the supernatant effectively. The intratumoral delivery of rAAV-VAS inhibited the xenograft growth and microvessel density in tumors significantly. Our results show the effectiveness of rAAV-VAS as an angiogenesis inhibitor in suppressing tumor growth, validating the application of rAAV-VAS gene therapy in treatment against colon cancer.
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Authors | Yong Diao, Jian Ma, Xinyan Li, Xueying Sun, Ruian Xu |
Journal | Sheng wu gong cheng xue bao = Chinese journal of biotechnology
(Sheng Wu Gong Cheng Xue Bao)
Vol. 24
Issue 11
Pg. 1949-54
(Nov 2008)
ISSN: 1000-3061 [Print] China |
PMID | 19256344
(Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Calreticulin
- Peptide Fragments
- Recombinant Proteins
- vasostatin
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Topics |
- Angiogenesis Inhibitors
(biosynthesis, genetics, pharmacology)
- Animals
- Calreticulin
(biosynthesis, genetics)
- Cell Proliferation
(drug effects)
- Colonic Neoplasms
(pathology)
- Dependovirus
(genetics, metabolism)
- Genetic Vectors
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Peptide Fragments
(biosynthesis, genetics)
- Recombinant Proteins
(biosynthesis, genetics, pharmacology)
- Tumor Cells, Cultured
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