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7094596 
Journal Article 
Aspirin attenuates vinorelbine-induced endothelial inflammation via modulating SIRT1/AMPK axis 
Tsai, KunL; Hsiao, CY; Chiou, SHwa; Chen, JawWen; Lin, SJ; Huang, PoH; Kao, CLan; Leu, HB; Cheng, YH; Liao, YiWen; Yang, YiP; Chien, Y; Wang, CY; , 
2014 
Yes 
Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968 
PERGAMON-ELSEVIER SCIENCE LTD 
OXFORD 
189-200 
24345330 
WOS:000332903600007 
Vinorelbine (VNR), a semisynthetic vinca alkaloid acquired from vinblastine, is frequently used as the candidate for intervention of solid tumors. Nevertheless, VNR-caused endothelial injuries may lead a mitigative effect of clinical treatment efficiency. A growing body of evidence reveals that aspirin is a potent antioxidant and anti-inflammation drug. We investigated whether aspirin attenuate VNR-induced endothelial dysfunction. Human endothelial cells (EA.hy 926) were treated with VNR to cause endothelial inflammation. Western blotting, ROS assay, ELISA were used to confirm the anti-inflammatory effect of aspirin. We confirmed that VNR supresses SIRT1 expression, reduced LKB1 and AMPK phosphorylation as well as enriched PKC activation in treated endothelial cells. Furthermore, the membrane translocation assay displayed that the levels of NADPH oxidase subunits p47phox and Rac-1 in membrane fractions of endothelial cells were higher in cells that had been treated with VNR for than in untreated cells. We corroborated that treatment of Aspirin significantly diminishes VNR-repressed SIRT1, LKB1 and AMPK phosphorylation and VNR-promoted NADPH oxidase activation, however, those findings were vanished by SIRT1 and AMPK siRNAs. Our data also shown that Aspirin represses VNR-activated TGF-beta-activated kinase-1 (TAK1) activation, inhibited the interaction of TAK1/TAK-binding protein1 (TAB1), suppressed NF-kappa B activation and pro-inflammatory cytokine secretion. We demonstrated a novel connection between VNR-caused oxidative damages and endothelial dysfunction, and provide further insight into the protective effects of aspirin in VNR-caused endothelial dysfunction. (C) 2014 Elsevier Inc. All rights reserved.