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

AIM:To determine the inhibitory effect of the adenovirusbased 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 adenovirustransfected 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.