title: Vascular endothelial growth factor-D promotes growth, lymphangiogenesis and lymphatic metastasis in gallbladder cancer.
abstract: 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.
authors.affiliation: Department of Hepatobiliary Surgery, Union Clinical Medical College, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Chen
authors.forename: Feifei
authors.initials: F
authors.lastname: She
authors.forename: Shenghua
authors.initials: S
authors.lastname: Han
authors.forename: Jinhai
authors.initials: J
authors.lastname: Zhu
authors.forename: Liangyi
authors.initials: L
authors.lastname: Zhou
authors.forename: Nanhong
authors.initials: N
authors.lastname: Tang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.forename: Xiujin
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005706:Gallbladder Neoplasms / Q000473:pathology*; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D051379:Mice; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D042643:Vascular Endothelial Growth Factor D / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042643:Vascular Endothelial Growth Factor D