title: Beclin1/PI3K-mediated autophagy prevents hypoxia-induced apoptosis in EAhy926 cell line.
abstract: Although hypoxia can induce cell death, the cancer cells and endothelial cells within a solid tumor that remain active in the hypoxia microenvironment often possess an enhanced survival potential. Developing approaches aimed at increasing the sensitivity of endothelial cells to hypoxia-induced cell death represents a potentially important avenue for antiangiogenesis treatment. This study investigated approaches to increase the sensitivity of endothelial cells to hypoxia-induced apoptosis. Autophagy and apoptosis of endothelial cells induced by hypoxia were investigated by transmission electron microscopy, confocallaser microscopy, and western blotting. Moreover, cell invasion was observed by a transwell assay and F-actin quantitative analysis. In this study, it was found that hypoxia could induce both autophagy and apoptosis in hypoxia-inducible factor-1- and Beclin1-dependent endothelial cells. Hypoxia-induced autophagy was prohibited by phosphatidylinositol 3-kinase/Akt inhibitor but not mitogen-activated protein kinase inhibitor. Inhibition of autophagy promoted the rate of apoptosis. Further, the reversal of hypoxia-induced autophagy increased cell migration compared with the normoxia condition. This study concludes that hypoxia triggers a feedback mechanism that delays apoptosis of endothelial cells and that is driven by hypoxia-induced autophagy. Thus, approaches aimed at the disruption of this mechanism can be expected to enhance the susceptibility of endothelial cells to hypoxia-induced apoptosis.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Ruiguang
authors.initials: R
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Zhu
authors.forename: Jinghua
authors.initials: J
authors.lastname: Ren
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.forename: Pian
authors.initials: P
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D000199:Actins / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D000860:Hypoxia / Q000473:pathology; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D053148:Caspase 3; C008542:monodansylcadaverine; D002103:Cadaverine