Inhibitory effect of paclitaxel on endothelial cell adhesion and migration.
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 microg/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.
Li
Hua
H
Department of Pathology and Pathophysiology, Basic Medical School of Wuhan University, Wuhan, China.
Zhang
Li-jun
LJ
Chen
Bai-hua
BH
Zhou
Xuan
X
Su
Ke
K
Shi
Wen-tao
WT
Wu
Jun-zhu
JZ
Yu
Hong
H
Wei
Lei
L
D002317:Cardiovascular Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D000098662:Vasodilator-Stimulated Phosphoprotein
D002317:Cardiovascular Agents; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017239:Paclitaxel