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World J Gastroenterol. Mar 14, 2008; 14(10): 1575-1581
Published online Mar 14, 2008. doi: 10.3748/wjg.14.1575
Angiopoietin-1 targeted RNA interference suppresses angiogenesis and tumor growth of esophageal cancer
Xiao-Hong Liu, Chen-Guang Bai, Yang Yuan, De-Jun Gong, Sheng-Dong Huang
Xiao-Hong Liu, Yang Yuan, De-Jun Gong, Sheng-Dong Huang, Institute of Thoracardiac Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Chen-Guang Bai, Department of Pathology, Changhai Hospita, Second Military Medical University, Shanghai 200433, China
Correspondence to: Sheng-Dong Huang, MD, PhD, Institute of Thoracardiac Surgery, Changhai Hospital, 174, Changhai Rd, Shanghai 200433, China. xxwkdaily@163.com
Telephone: +86-21-25072079
Fax: +86-21-65490979
Received: June 15, 2007
Revised: November 28, 2007
Published online: March 14, 2008
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.

Keywords: Angiopoietin-1, Angiogenesis, Esophageal cancer, RNA Interference, Cancer