Celecoxib could reverse the hypoxia-induced Angiopoietin-2 upregulation in gastric cancer.
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.
Wang
Jun
J
State Key Laboratory of Cancer Biology and Institute of Digestive Disease, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Wu
Kaichun
K
Bai
Feihu
F
Zhai
Huihong
H
Xie
Huahong
H
Du
Yulei
Y
Liang
Jie
J
Han
Shuang
S
Chen
Yu
Y
Lin
Tao
T
Fan
Daiming
D
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
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