血管生成素-1靶向RNA干扰抑制食管癌的血管生成和肿瘤生长。

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

作者信息

Liu Xiao-Hong, Bai Chen-Guang, Yuan Yang, Gong De-Jun, Huang Sheng-Dong

机构信息

Institute of Thoracardiac Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

出版信息

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

DOI:10.3748/wjg.14.1575

PMID:18330951

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2693755/

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.

摘要

目的

确定基于腺病毒的血管生成素-1（Ang-1）靶向小干扰RNA表达系统（Ad/Ang-1si）对人食管癌Eca109细胞系中Ang-1基因表达、细胞生长及凋亡的抑制作用。

方法

利用Ad Easy系统构建靶向Ang-1基因的表达小干扰RNA的腺病毒。用Ad/Ang-1si转染培养的Eca109细胞（Eca109/Ang-1si），并用Ad/si感染Eca109细胞作为对照（Eca109/si）。分别用逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）法测定Ang-1基因表达及浓度。分析人脐静脉内皮细胞（HUVEC）的迁移和增殖情况。将细胞皮下注射到无胸腺裸鼠体内后，还测定了每组的肿瘤生长、血管密度及凋亡情况。

结果

由Ang-1si转染的Eca109细胞的条件培养基诱导的HUVEC迁移明显少于Eca109细胞及对照腺病毒转染的Eca109细胞的条件培养基诱导的迁移。此外，皮下注射到无胸腺裸鼠体内后，表达Ad/Ang-1si的Eca109细胞的肿瘤生长及细胞凋亡明显低于亲本细胞或对照腺病毒转染的细胞。通过CD31免疫组织化学分析评估的血管密度及RT-PCR检测的Ang-1表达也降低。