Vascular endothelial growth factor-D promotes growth, lymphangiogenesis and lymphatic metastasis in gallbladder cancer

被引:28
作者
Lin, Wei [1 ]
Jiang, Lei [1 ]
Chen, Yanling [1 ]
She, Feifei [2 ]
Han, Shenghua [1 ]
Zhu, Jinhai [1 ]
Zhou, Liangyi [1 ]
Tang, Nanhong [1 ]
Wang, Xiaoqian [1 ]
Li, Xiujin [1 ]
机构
[1] Fujian Med Univ, Dept Hepatobiliary Surg, Union Clin Med Coll, Fuzhou 350001, Peoples R China
[2] Fujian Med Univ, Dept Pathogen Microorganism, Coll Basic Med Sci, Fuzhou 350004, Peoples R China
关键词
Gallbladder cancer; VEGF-D; Growth; Lymphangiogenesis; Metastasis; FACTOR-D EXPRESSION; VEGF-C; COLORECTAL-CARCINOMA; RNA INTERFERENCE; NODE METASTASIS; TUMOR LYMPHANGIOGENESIS; GASTRIC-CARCINOMA; MAMMALIAN-CELLS; FACTOR FAMILY; GENE-FUNCTION;
D O I
10.1016/j.canlet.2011.09.004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Lymph node metastasis is a major prognostic factor for patients with gallbladder cancer (GBC), and greater understanding of the molecule mechanism of lymph node metastasis in GBC is needed to improve prognosis. VEGF-D has been implicated in the control of lymphangiogenesis in many carcinomas, but the biological function of VEGF-D in human GBC remains unclear. In this study, we analyzed the role of the VEGF-D in human GBC cells and addressed the functional role of VEGF-D using a xenograft mouse model. We examined the expression of VEGF-D in three human gallbladder cancer cell lines. A lentivirus-based effective VEGF-D siRNA vector was infected into GBC NOZ cells. The effect of VEGF-D siRNA on GBC NOZ cells was investigated by cell proliferation assay and invasion assay. Furthermore, we examined the role of VEGF-D-SiRNA on GBC NOZ cells in the mice of subcutaneous and orthotopic xenograft tumor. Our results are as follows: VEGF-D mRNA and protein were expressed in all three GBC cell lines (GBC-SD. NOZ, and SGC-996). We successfully selected D-3/siRNA as the most effective siRNA to silence VEGF-D expression after four VEGF-D siRNA plasmid transfection in NOZ cells. VEGF-D mRNA and protein expression were suppressed by lentivirus-mediated D-3/siRNA. D-3-RNAi-LV inhibited NOZ cells proliferation and invasion ability in vitro. D-3-RNAi-LV inhibited tumor growth and lymphangiogenesis in the NOZ cell subcutaneous xenograft model. D-3-RNAi-LV inhibited lymphangiogenesis and lymphatic metastasis in the NOZ cell orthotopic xenograft model. Furthermore, D-3-RNAi-LV inhibited tumor ascites and hepatic invasion in the NOZ cell orthotopic xenograft model. In conclusion, VEGF-D is involved and plays an important role in GBC progression, suggesting that VEGF-D may be a potential molecular target in the treatment of GBC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:127 / 136
页数:10
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