A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin

F. Xiao, Y. Wei, L. Yang, X. Zhao, L. Tian, Z. Ding, S. Yuan, Y. Lou, F. Liu, Y. Wen, J. Li, H. Deng, B. Kang, Y. Mao, S. Lei, Q. He, J. Su, Y. Lu, T. Niu, J. HouM. J. Huang

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

The growth and persistence of solid tumors and their metastasis are angiogenesis-dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is a potent angiogenesis inhibitor. To investigate whether intramuscular administration of vasostatin gene has the anti-tumor activity in mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a control vector. Production and secretion of vasostatin protein by COS cells transfected with the plasmid DNA encoding vasostatin (pSecTag2B-vaso) were confirmed by Western blot analysis and ELISA. Conditioned medium from vasostatin-transfected COS cells apparently inhibited human umbilical vein endothelial cell (HUVEC) and mouse endothelial cell (SVEC4-10) proliferation, compared with conditioned medium from the COS cells transfected with control vector or non-transfected cells. Treatment with pSecTag2B-vaso twice weekly for 4 weeks resulted in the inhibition of tumor growth and the prolongation of the survival of tumor-bearing mice. The sustained high level of vasostatin protein in serum could be identified in ELISA. Angiogenesis was apparently inhibited in tumor by immunohistochemical analysis. Angiogenesis was also inhibited in the chicken embryo CAM assay and mouse corneal micropocket assay. The increased apoptotic cells were found within the tumor tissues from the mice treated with plasmid DNA encoding vasostatin. Taken together, the data in the present study indicate that the cancer gene therapy by the intramuscular delivery of plasmid DNA encoding vasostatin, is effective in the inhibition of the systemic angiogenesis and tumor growth in murine models. The present findings also provide further evidence of the anti-tumor effects of the vasostatin, and may be of importance for the further exploration of the application of this molecule in the treatment of cancer.

Original languageEnglish (US)
Pages (from-to)1207-1213
Number of pages7
JournalGene Therapy
Volume9
Issue number18
DOIs
StatePublished - Sep 2002

Keywords

  • Angiogenesis
  • Dna plasmid
  • Gene therapy
  • Vasostatin

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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  • Cite this

    Xiao, F., Wei, Y., Yang, L., Zhao, X., Tian, L., Ding, Z., Yuan, S., Lou, Y., Liu, F., Wen, Y., Li, J., Deng, H., Kang, B., Mao, Y., Lei, S., He, Q., Su, J., Lu, Y., Niu, T., ... Huang, M. J. (2002). A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin. Gene Therapy, 9(18), 1207-1213. https://doi.org/10.1038/sj.gt.3301788