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


CONCLUSIONS
The targeting Ang-1 may provide a therapeutic option for esophageal cancer.
Liu
Xiao-Hong
XH
Institute of Thoracardiac Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Bai
Chen-Guang
CG
Yuan
Yang
Y
Gong
De-Jun
DJ
Huang
Sheng-Dong
SD
D042683:Angiopoietin-1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics*; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D034741:RNA, Small Interfering