title: Celecoxib could reverse the hypoxia-induced Angiopoietin-2 upregulation in gastric cancer.
abstract: We investigated the potential effect of Cyclooxygenase-2 (Cox-2) on hypoxia-induced Angiopoietin-2 (Ang-2) expression in gastric cancer cells. Our results revealed that hypoxia augmented Cox-2 and Ang-2 expressions. Also, the hypoxia-induced Ang-2 could be mimicked by CoCl(2) treatment while genestein treatment could partially counteract the hypoxia-induced Ang-2 expression. Celecoxib but not Cox-1 inhibitor sc-560 reversed the hypoxia-induced Ang-2 expression, while this effect could be partially restored by addition of exogenous PGE2. Our findings suggest that the hypoxia-elevated Ang-2 expression in gastric cancer cells may be mediated by both Cox-2-derived PGE2 and HIF-1alpha pathways, while celecoxib could counteract the hypoxia-induced Ang-2 expression.
authors.affiliation: State Key Laboratory of Cancer Biology and Institute of Digestive Disease, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Feihu
authors.initials: F
authors.lastname: Bai
authors.forename: Huihong
authors.initials: H
authors.lastname: Zhai
authors.forename: Huahong
authors.initials: H
authors.lastname: Xie
authors.forename: Yulei
authors.initials: Y
authors.lastname: Du
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.forename: Shuang
authors.initials: S
authors.lastname: Han
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D042702:Angiopoietin-2 / Q000096:biosynthesis*; D042682:Angiopoietins / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D042702:Angiopoietin-2; D042682:Angiopoietins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone