Dynamic distribution and expression in vivo of human endostatin gene delivered by adenoviral vector

Life Sci. 2005 Aug 5;77(12):1331-40. doi: 10.1016/j.lfs.2005.01.023.

Abstract

Endostatin, a 20-kDa carboxyl-terminal fragment of collagen XVIII, is a potent inhibitor of endothelial cell proliferation and tumor angiogenesis. We have constructed replication-deficient recombinant adenovirus (Ad-rhE), which encoded secreted human endostatin, and our previous studies showed that Ad-rhE had a potent suppression of tumor growth in vivo. In the present study, we investigated the dynamic distribution and expression of human endostatin gene in vivo using fluorogenic real-time quantitative PCR and enzyme-linked immunosorbent assay(ELISA), respectively, with an injection of 2.0 x10(9)pfu of Ad-rhE. After injection, the Ad-rhE DNAs decreased sharply, but lasted a relative long-term at low concentration (10,000--20,000 copies/mg tissues). Whereas the expressed endostatin rose up rapidly, and reached to the top on day 5 after injection of Ad-rhE, and then decreased sharply, but endostatin in tumors sustained to over 9 days at a certain level. Both Ad-rhE DNAs and endostatin mainly enriched in tumors in vivo, and then in livers. These results suggest that endostatin gene delivered by adenoviral vector can generate a high expression in vivo, and both the metabolism pathways of Ad-rhE DNAs and endostatin in vivo are through the systems of livers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Cell Line, Tumor
  • Endostatins / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression
  • Gene Transfer Techniques
  • Humans
  • Injections
  • Liver / metabolism
  • Melanoma, Experimental / metabolism
  • Neoplasm Transplantation
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Endostatins