Inhibitory Effect of Paclitaxel on Endothelial Cell Adhesion and Migration

Abstract

The long-term success of percutaneous coronary interventions has been limited by restenosis. Therefore, local delivery of paclitaxel, an antiproliferative agent, using drug-eluting stents has been applied to prevent in-stent restenosis. However, paclitaxel not only inhibits smooth muscle cell proliferation, but also delays re-endothelialization of the damaged site, which may cause potentially life-threatening cardiovascular adverse events, especially late and very late stent thrombosis. We investigated the role of paclitaxel in endothelial cell line ECV304 adhesion and migration. Accordingly, changes in vasodilator-stimulated phosphoprotein protein (VASP) phosphorylation and cAMP-dependent protein kinase activity during ECV304 cell detachment and reattachment were investigated as well. The results showed that the decrease in VASP phosphorylation paralleled the inhibition of cAMP-dependent protein kinase (PKA) activity in the presence of paclitaxel (10 µg/l). Cell adhesion assay and two- and three-dimensional cell migration assays were performed to determine the effect of paclitaxel on the adhesion and migration of ECV304 cells. Paclitaxel significantly suppresses the adhesion (p < 0.05) and migration of ECV304 cells (p < 0.05). These data suggest that the inhibitory effect of paclitaxel may be produced by decreasing the phosphorylation of VASP via inhibition of PKA activity during ECV304 cell adhesion and migration.

Reduction in Migratory Phenotype in a Metastasized Breast Cancer Cell Line via Downregulation of S100A4 and GRM3

“…Paclitaxel treatment increased passing time in the channel, reduced S100A4, and inhibited TMD’s migratory ability. Our observation is consistent with an inhibitory role of Paclitaxel 18 as well as a stimulatory role of S100A4 and GRM3 in cell adhesion and migration.…”

“…Furthermore, a microfluidic assay was employed to characterize cellular motility in the presence and absence of Paclitaxel 16–18 .…”

The zebrafish ventricle: A hub of cardiac endothelial cells for in vitro cell behavior studies

“…As proof of principle, we chose to test Paclitaxel, a microtubule stabilizer that inhibits endothelial cell migration 20 , and vascular endothelial growth factor (VEGF) that induces EC migration by promoting filamentous actin structure formation 21 . Cells from a 2 nd passage were cultured with 10% FBS to establish a monolayer and then serum and VEGF starved for 6 h. Subsequently, cells were treated with DMSO (control), or with a medium containing VEGF (same concentration as in EGM2), or with paclitaxel (12 nM final concentration).…”

Intravenous Administration of High-Dose Paclitaxel Reduces Gut-Associated Lymphoid Tissue Cell Number and Respiratory Immunoglobulin A Concentrations in Mice

“…To the contrary, we previously reported administration of 5-fluorouracil (5-FU), an inhibitor of thymidylate synthese, to reduce lymphocyte numbers in IE spaces and LP without marked changes in PP lymphocyte number [23]. Second, PTX may have lowered adhesion-molecule expression on the high endothelial venules of PP, leading to reduction of PP cell number, because PTX reportedly exerts inhibitory effects on endothelial-cell adhesion and migration [24]. In therapy for coronary artery disease, PTX drug-eluting stents prevent in-stent re-stenosis by inhibiting endothelialcell adhesion and migration [25].…”