title: Docetaxel inhibits cyclooxygenase-2 induction in vascular smooth muscle cells.
abstract: The aim of this study was to determine whether docetaxel affects expression of cyclooxygenase-2 (COX-2) in vascular smooth muscle cells. Cultured rat aortic smooth muscle cells (RASMCs) were stimulated with interleukin-1b (IL-1β). COX-2 expression level and ERK activity were evaluated by Western blot analysis. COX-2 expression as well as tubulin formation was also evaluated by immunocytochemical analysis. IL-1β induced COX-2 expression in RASMCs, which was inhibited by docetaxel (5-20µg/ml) in a concentration-dependent manner. IL-1β increased ERK activity, which was not affected by docetaxel. IL-1β-induced COX-2 expression level was markedly augmented at 24h after washing out docetaxel from the culture medium. Immunocytochemical analysis revealed that COX-2 immunoreactivity in RASMCs stimulated with IL-1β was decreased in the presence of docetaxel but was recovered at 24h after washing out docetaxel, while docetaxel-induced change in tubulin formation, namely, polymerization of α-tubulin fibers, remained at 24h after washing out docetaxel. The results suggest that docetaxel inhibits COX-2 induction, and this action of docetaxel is reversible and ERK-independent.
authors.affiliation: Department of Environmental and Preventive Medicine, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakano
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Wakabayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000378:metabolism; D000077143:Docetaxel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002070:Butadienes; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D009570:Nitriles; D043823:Taxoids; C113580:U 0126; D000077143:Docetaxel; D051546:Cyclooxygenase 2; D048052:Mitogen-Activated Protein Kinase 3