In vitro paclitaxel and radiation effects on the cell types responsible for vascular stenosis: a preliminary analysis.
Hemodialysis vascular access dysfunction as a result of venous neointimal hyperplasia in dialysis access grafts and fistulae is currently a huge clinical problem. The aim of this study was to assess the effects of paclitaxel and radiation, both singly and in combination on the proliferation of cell types present within the lesion of venous neointimal hyperplasia (vascular smooth muscle cells, fibroblasts and endothelial cells within the neointimal microvessels). Vascular smooth muscle cells, fibroblasts and endothelial cells were plated onto 96-well plates and exposed to different concentrations and doses of paclitaxel and radiation, respectively (both individually and in combination). Growth inhibition was assessed with an MTT assay. Both paclitaxel and radiation resulted in significant growth inhibition of all three cell types. However, even small doses of paclitaxel appeared to attenuate the antiproliferative effect of radiation on these cell types. Further experiments to elucidate the mechanism behind these findings could result in a better understanding of combination antiproliferative therapies.
Zhang
J
J
Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0585, USA.
Melhem
M
M
Kassing
W
W
Kelly
B
B
Wang
Y
Y
Krishnamoorthy
M
M
Heffelfinger
S
S
Desai
P
P
Roy-Chaudhury
P
P
D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D017239:Paclitaxel / Q000494:pharmacology*
D017239:Paclitaxel