Angiopoietin-1 targeted RNA interference suppresses angiogenesis and tumor growth of esophageal cancer

World J Gastroenterol. 2008 Mar 14;14(10):1575-81. doi: 10.3748/wjg.14.1575.

Abstract

Aim: To determine the inhibitory effect of the adenovirus-based angiopoietin-1 (Ang-1) targeted small interfering RNA expression system (Ad/Ang-1si) on the expression of the Ang-1 gene, cell growth and apoptosis in human esophageal cancer cell line Eca109.

Methods: siRNA-expressing adenovirus targeting Ang-1 gene was constructed using the Ad Easy System. Cultured Eca109 cells were transfected with Ad/Ang-1si (Eca109/Ang-1si), and Ad/si was used to infect Eca109 cells as control (Eca109/si). Ang-1 gene expression and concentration was determined with RT-PCR and ELISA, respectively. Human umbilical vein endothelial cell (HUVEC) migration and proliferation were analyzed. After s.c. injection into athymic nu/nu mice, the tumor growth, vessel density and apoptosis of each group was also determined.

Results: HUVEC migration induced by conditioned medium from Ang-1si-transfected Eca109 cells was significantly less than that induced by conditioned medium from Eca109 cells and control adenovirus-transfected Eca109 cells. Furthermore, after s.c. injection into athymic nu/nu mice, the tumor growth and cell apoptosis of Ad/Ang-1si -expressing Eca109 cells was significantly lower than that of parental or control adenovirus-transfected cells. Vessel density assessed by CD31 immunohistochemical analysis and Ang-1 expression by RT-PCR were also decreased.

Conclusion: The targeting Ang-1 may provide a therapeutic option for esophageal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / genetics*
  • Angiopoietin-1 / metabolism
  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Esophageal Neoplasms / blood supply*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / therapy
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / genetics*
  • RNA Interference / physiology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • ANGPT1 protein, human
  • Angiopoietin-1
  • RNA, Small Interfering