Jakub Wiskirchen MD, Abstract Co-Author: Nothing to Disclose

Sascha Khorchidi, Abstract Co-Author: Nothing to Disclose

Rainer Kehlbach, Abstract Co-Author: Nothing to Disclose

Gunnar Tepe MD, Presenter: Nothing to Disclose

Claus Detlef Claussen MD, Abstract Co-Author: Nothing to Disclose

Stephan Hoyt Duda MD, Abstract Co-Author: Nothing to Disclose

The aim of the study was to compare the growth modulating potential of Paclitaxel (PTX) and Combretastatin A-4 (CA-4) on cultured human aortic smooth muscle and endothelial cells depending on the administered dose.

For all experiments human aortic smooth muscle cells (SMC) and endothelial cells (EC) were used. SMC and EC were either treated for 4 or for 20 days with either PTX or CA-4 (doses: 5x10-10M, 2.5x10-9M, 5x10-9M). For a period of 20 days proliferation kinetics were analyzed. To assess the clonogenic activity of the SMC colony formation assays were performed. Drug and dose dependant cell cycle changes were analyzed by flow cytometry. Additionally, western blots were performed to evaluate the effect of PTX and CA-4 treatment on cell cycle regulating proteins.

Depending on the dose administered, both drugs inhibited SMC and EC proliferation. However, CA-4 proved to be much more effective than PTX at the doses administered. In contrast to PTX a single dose of CA-4 was sufficient to inhibit SMC growth effectively. No colonies were formed after treatment with a CA-4 dose of 5x10-9M. Flow cytometry revealed a G2/M phase block for the 5x10-9M CA-4 groups, whereas cell cycle changes were only slight for the PTX groups The intracellular content of Cyclin D1 and D2, Cyclin E and A was lower, the content of P27 higher in the treated SMC compared to the controls for both drugs, suggesting a G1 phase blockage. Both drugs also inhibited EC growth effectively.

In vitro Combretastatin A-4 proved to be much more effective in inihibiting SMC proliferation than Paclitaxel. In vivo Combretastatin A-4 might possibly be helpful in fighting restenosis formation following angioplasty. As knowledge about the interaction of CA-4 with SMC and EC still is limited, further research is mandatory.

Wiskirchen, J, Khorchidi, S, Kehlbach, R, Tepe, G, Claussen, C, Duda, S, Comparison of the Growth Modulating Effects of the Antiproliferative Drugs Paclitaxel and Combretastatin A-4 on Cultured Human Aortic Smooth Muscle and Endothelial Cells.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4414550.html