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[Construction and activity of recombinant adeno-associated virus expressing vasostatin].

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.
AuthorsYong Diao, Jian Ma, Xinyan Li, Xueying Sun, Ruian Xu
JournalSheng 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
PMID19256344 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Calreticulin
  • Peptide Fragments
  • Recombinant Proteins
  • vasostatin
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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