title: VEGF Silencing Inhibits Human Osteosarcoma Angiogenesis and Promotes Cell Apoptosis via PI3K/AKT Signaling Pathway.
abstract: Vascular endothelial growth factor (VEGF) is one of the most effective angiogenic factors that promote generation of tumor vasculature. VEGF is usually up-regulated in multiple cancers including osteosarcoma and glioma. To further explore the potential molecular mechanism that inhibits tumor growth induced by interference of VEGF expression, we constructed a Lv-shVEGF vector and assessed the efficiency of VEGF silencing and its influence in U2OS cells. The data demonstrate that Lv-shVEGF has high inhibition efficiency on VEGF expression, which inhibits proliferation and promotes apoptosis of U2OS cells in vitro. Our results also indicate that inhibition of VEGF expression suppresses osteosarcoma tumor growth in vivo and reduces osteosarcoma angiogenesis. We also found that the activations of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) were considerably reduced after osteosarcoma cells were treated with Lv-shVEGF. Taken together, our data demonstrate that VEGF silencing suppresses cell proliferation, promotes cell apoptosis, and reduces osteosarcoma angiogenesis through inactivation of PI3K/AKT signaling pathway.
authors.affiliation: Department of Orthopedic Surgery, Tangdu Hospital, Orthopedics Oncology Institute of Chinese PLA, Fourth Military Medical University, NO 569 XinSi Road, Xi'an, 710038, Shanxi Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic Surgery, Tangdu Hospital, Orthopedics Oncology Institute of Chinese PLA, Fourth Military Medical University, NO 569 XinSi Road, Xi'an, 710038, Shanxi Province, China.
authors.forename: Zi-Ru
authors.initials: ZR
authors.lastname: Zhang
authors.affiliation: Outpatient Department, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, Shanxi Province, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic Surgery, Tangdu Hospital, Orthopedics Oncology Institute of Chinese PLA, Fourth Military Medical University, NO 569 XinSi Road, Xi'an, 710038, Shanxi Province, China.
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Ma
authors.affiliation: Department of Orthopedic Surgery, Tangdu Hospital, Orthopedics Oncology Institute of Chinese PLA, Fourth Military Medical University, NO 569 XinSi Road, Xi'an, 710038, Shanxi Province, China. drfanqingyu01@163.com.
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D009389:Neovascularization, Pathologic; D012516:Osteosarcoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Angiogenesis; Cell apoptosis; Lentivirus-mediated short hairpin RNA (Lv-shRNA); U2OS cells; Vascular endothelial growth factor (VEGF)