title: Lentivirus-mediated shRNA interference targeting vascular endothelial             growth factor inhibits angiogenesis and progression of human pancreatic carcinoma.
abstract: Angiogenesis is known to be essential to the survival, growth, invasion             and metastasis of cancer cells. Vascular endothelial growth factor (VEGF) is an             important factor regulating tumor angiogenesis. In the present study, we analyzed             the effect of lentivirus-mediated shRNA interference targeting vascular endothelial             growth factor (VEGF) on angiogenesis and progression in the pancreatic cancer             cell line Patu8988 in vitro and in vivo. The study aimed to construct a recombinant             lentivirus carrying targeted VEGF shRNA (LV-RNAi) to be used to transfect Patu8988             cells, and we investigated its anti-angiogenic and growth inhibitory effects on             pancreatic cancer. VEGF expression was measured by RQ-PCR, western blotting and             enzyme-linked immunosorbent assay (ELISA). In subcutaneous transplantation models,             tumor volumes were determined, and the expression levels of VEGF and CD34 were             assessed by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated             dUTP nick-end labeling (TUNEL) was used to determine apoptosis. In the orthotopic             transplantation models, tumor volume and liver metastasis were determined. We             successfully constructed LV-RNAi and confirmed that it knocked down the VEGF gene             at the mRNA and protein levels in Patu8988 cells. In the subcutaneous transplantation             models, tumors with low levels of VEGF expression exhibited reduced pancreatic             carcinoma angiogenesis and growth, and the apoptotic index was significantly higher.             In the orthotopic transplantation models, tumors with low levels of VEGF expression             exhibited significantly reduced pancreatic carcinoma growth, but no significant             difference was observed between the three mouse groups, LV-RNAi, LV-NC and the             control, in regards to liver metastasis. In summary, lentivirus-mediated RNAi             silencing of VEGF inhibited tumor angiogenesis and growth, and increased apoptosis             of the pancreatic cancer cell line Patu8988. VEGF targeted gene silencing approach             has the potential to serve as a novel treatment for pancreatic cancer.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Zhu
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Gan
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Jiang-Lei
authors.initials: JL
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: De-Chun
authors.initials: DC
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008113:Liver Neoplasms / Q000098:blood supply / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014162:Transfection; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A