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.