title: RNAi-mediated gene silencing of vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of gastric cancer in vivo in mice.
abstract: Overexpression of vascular endothelial growth factor-C (VEGF-C) has been implicated as a critical molecular signal in tumor development by promoting intratumoral lymphangiogenesis. The aim of this study was to explore whether small hairpin RNA (shRNA) targeting VEGF-C could inhibit gastric cancer lymphangiogenesis and tumor growth. Plasmid-mediated expression of VEGF-C-shRNA was employed to silence VEGF-C gene expression in human SGC-7901 cell lines. The inhibition of the target gene expression was quantified by real-time quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. In vitro, the cell viability was determined by MTT assay, flow cytometry analysis, and migration assay. After VEGF-C knockdown was confirmed, the stable cells were inoculated into nude mice. Tumor growth, lymph vessel density (LVD), and microvascular density were compared for mice administered either VEGF-C-shRNA or control. VEGF-C-shRNA causes effective and specific downregulation of VEGF-C expression (P<0.05). The migration activity of SGC-7901 cells was attenuated in vitro (P<0.05). Tumor growth rate and LVD was suppressed in vivo (P<0.05). VEGF-C-shRNA effectively suppressed gastric cancer cell migration in vivo, retards tumorigenicity, and lymphangiogenesis in nude mice.
authors.affiliation: Department of Surgery, Ningxia Medical University, Yingchuan, People's Republic of China.
authors.forename: Jibin
authors.initials: J
authors.lastname: Yao
authors.forename: Mingxu
authors.initials: M
authors.lastname: Da
authors.forename: Tiankang
authors.initials: T
authors.lastname: Guo
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Duan
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020868:Gene Silencing; D005822:Genetic Vectors; D006801:Humans; D007124:Immunoenzyme Techniques; D042583:Lymphangiogenesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C