title: Silencing of VEGF inhibits human osteosarcoma angiogenesis and promotes cell apoptosis via VEGF/PI3K/AKT signaling pathway.
abstract: BACKGROUND
  Osteosarcoma is a kind of highly malignant tumor and the growth and metastasis is closely related to angiogenesis. Vascular endothelial growth factor (VEGF) is an important angiogenesis-promoting factor. In the current study, we investigated the effects of suppressed VEGF on osteosarcoma and its molecular mechanism provided for a basis by targeting angiogenesis.
  
  
  METHODS
  We established bearing human osteosarcoma Wistar rats model by subcutaneous inoculation of human SaOS-2 cells and the adenovirus vector Ad-VEGF-siRNA was constructed for further study. We assessed the efficiency of VEGF silencing and its influence on SaOS-2 cells. The expression of mRNA and protein were detected by RT-PCR and western blotting, respectively. Intratumoral microvessel density (MVD), VEGF and CD31 were evaluated by immunohistochemistry. We detected the cell apoptotic rates by flow cytometry.
  
  
  RESULTS
  Our results indicated that Ad-VEGF-siRNA could effectively suppressed the expression of VEGF expression, inhibited the proliferation capability and promoted apoptosis of SaOS-2 cells in vitro. Silencing of VEGF expression also suppress osteosarcoma tumor growth and reduce osteosarcoma angiogenesis in the Wistar rats model in vivo. Furthermore, We found that phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) activation were considerably reduced while inhibition VEGF expression in SaOS-2 cells.
  
  
  CONCLUSIONS
  Our data demonstrated that VEGF silencing could suppress cells proliferation, promote cells apoptosis and reduce osteosarcoma angiogenesis through inactivation of VEGF/PI3K/AKT signaling pathway.
authors.affiliation: Department of Orthopaedic, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Peng
authors.affiliation: Department of Orthopaedic, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Orthopaedic, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Endocrinology, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.
authors.forename: Guangya
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedic, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopaedic, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.
authors.forename: Kehun
authors.initials: K
authors.lastname: Liu
keywords: Osteosarcoma; adenovirus; angiogenesis; siRNA; vascular endothelial growth factor (VEGF)