title: Lentivirus-Mediated RNAi Silencing of VEGF Inhibits Angiogenesis and Growth of Renal Cell Carcinoma in a Nude Mouse Xenograft Model.
abstract: To construct and screen short hairpin RNA (shRNA) targeting vascular endothelial growth factor (VEGF), and investigate potential values of VEGF-shRNA on angiogenesis and growth in renal cell carcinoma (RCC) in a xenograft tumor model. VEGF-shRNA fragment was designed to connect plasmid vector, and RCC cells were transfected with shRNA. Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) was used to detect interference efficiency of VEGF gene. The xenograft tumor model was established in nude mice, and mice were randomly divided into blank control (BC) group, negative control (NC) group, and experimental group. RNA interference (RNAi) effect was detected by immunohistochemistry, and tumor volume changes were observed. Tumor-bearing nude mice model was established and mice were randomly divided into BC group, NC group, and treatment group. The tumor volume changes and tumor inhibition rate were recorded, and angiogenesis status was observed. The apoptosis of tumor cells and genetic toxicity of VEGF-shRNA were detected. VEGF-shRNA can inhibit VEGF mRNA expression with an inhibition ratio of 72.3%. Compared with NC group and BC group, experimental group presents smaller tumor volume, weight, and poor growth (all p < 0.05). Positive VEGF rate in experimental group is significantly lower than that in NC group and BC group (all p < 0.05). Significantly lower tumor volume, less microvessel density (MVD) value, and higher apoptotic index (AI) are found in treatment group compared with BC group and NC group (all p < 0.05). There was no significant difference in AI between treatment group and BC group regarding adjacent normal tissues (p > 0.05). VEGF plays an important role in the occurrence and development of RCC, chemical synthesis of VEGF small interfering RNA (siRNA) can specifically inhibit VEGF expression, angiogenesis and growth in RCC, and can promote cell apoptosis without genetic toxicity to normal tissues.
authors.affiliation: 1 Cadet Brigade, The Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Jiahua
authors.initials: J
authors.lastname: Lin
authors.affiliation: 2 Department of Oncology, Tangdu Hospital, The Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Hailin
authors.initials: H
authors.lastname: Pang
authors.affiliation: 1 Cadet Brigade, The Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Guo
authors.affiliation: 1 Cadet Brigade, The Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Ding
authors.affiliation: 1 Cadet Brigade, The Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Jiaxu
authors.initials: J
authors.lastname: Geng
authors.affiliation: 1 Cadet Brigade, The Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Jingmeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 2 Department of Oncology, Tangdu Hospital, The Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Jie
authors.initials: J
authors.lastname: Min
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000473:pathology*; D020868:Gene Silencing; D005822:Genetic Vectors; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000473:pathology*; D016086:Lentivirus / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D008156:Luciferases