title: Arsenic induces the expressions of angiogenesis-related factors through PI3K and MAPK pathways in SV-HUC-1 human uroepithelial cells.
abstract: Arsenic, a well-established human carcinogen, can cause various types of cancers, including bladder cancer. Angiogenesis is a key event for tumor initiation. In this study, several important angiogenesis related factors, including cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α), were up-regulated and PI3K/AKT and MAPK signal pathways were activated in human uroepithelial cell line (SV-HUC-1) treated with NaAsO2 (0, 1, 2, 4, 8 or 10μM) for 24h. Arsenite-induced HIF-1α, VEGF and COX-2 expressions were decreased by PI3K inhibitors. Blockage of the ERK1/2, p38 and JNK down-regulated the VEGF level, while ERK1/2 and p38 inhibitors were more effective than JNK in attenuating arsenite-induced COX-2 expression. HIF-1α expression was only decreased by ERK1/2 inhibitor. It was found that superoxide (O2(-)) generation was involved in arsenite-induced the activation of MAPK and PI3K pathways, which led to the HIF-1α, COX-2 and VEGF overexpressions. In conclusion, arsenite-induced COX-2, VEGF and HIF-1α expressions, mediated partially by reactive oxygen species (ROS), were regulated by MAPK and PI3K/AKT signaling pathways in human uroepithelial cells.
authors: Department of Occupational and Environmental Health, Liaoning Provincial Key Lab of Arsenic Biological Effect and Poisoning, School of Public Health, China Medical University, No. 92 Bei Er Road, Heping District, Shenyang 110001, China.
authors: Fei
authors: F
authors: Wang
authors: Shengnan
authors: S
authors: Liu
authors: Shuhua
authors: S
authors: Xi
authors: Ling
authors: L
authors: Yan
authors: Huihui
authors: H
authors: Wang
authors: Yingli
authors: Y
authors: Song
authors: Guifan
authors: G
authors: Sun
mesh_terms: D020261:Arsenic Poisoning / Q000378:metabolism* / Q000503:physiopathology; D018053:Arsenites / Q000633:toxicity*; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D018053:Arsenites; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019869:Phosphatidylinositol 3-Kinases; C015001:arsenite
keywords: Arsenite; COX-2; HIF-1α; MAPK; PI3K/AKT; VEGF