The effects of paclitaxel on the three phases of restenosis: smooth muscle cell proliferation, migration, and matrix formation: an in vitro study.
OBJECTIVE
We sought to evaluate the growth-modulating potential of paclitaxel on cultured human arterial smooth muscle cells depending on the administered dose.


METHODS
For all experiments human arterial smooth muscle cells (SMCs) were used. SMCs were either cultured for 5 days or for 20 days with paclitaxel (doses: 10(-7) M, 10(-8) M, 10(-9) M). For a total period of 20 days, proliferation kinetics of the SMC were analyzed. To assess the clonogenic activity of the SMC colony-forming assays were performed. Drug- and dose-dependent cell cycle changes were analyzed by flow cytometry. The effect on cell migration was examined in a 2-chamber migration system. The effects of paclitaxel on the synthesis of tenascin were examined via immunofluorescence.


RESULTS
Depending on the dose administered, paclitaxel proved to inhibit SMC proliferation effectively when administered during the total period of 20 days. When incubated for 5 days with doses of paclitaxel ranging between 10(-8) M and 10(-9) M, SMCs showed clear signs of regeneration. When being incubated with 10(-7) M of paclitaxel, however, SMCs reacted with a reduction in cell proliferation, a reduced clonogenic activity, and a drug-induced G2/M phase block. SMC migration was inhibited effectively as well as extracellular matrix formation.


CONCLUSIONS
Paclitaxel is a potent inhibitor of SMC proliferation, SMC migration, and extracellular matrix formation in vitro, with all three phases of the restenosis process inhibited effectively.
Department of Diagnostic Radiology, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. jakub.wiskirchen@med.uni-tuebingen.de
Jakub
J
Wiskirchen
Wolfgang
W
Schöber
Nadine
N
Schart
Rainer
R
Kehlbach
Annika
A
Wersebe
Gunnar
G
Tepe
Claus D
CD
Claussen
Stephan H
SH
Duda
D000800:Angioplasty, Balloon; D001158:Arteries / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003251:Constriction, Pathologic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D012008:Recurrence; D019063:Tenascin / Q000096:biosynthesis*
D019063:Tenascin; D017239:Paclitaxel