Paclitaxel inhibits ureteral smooth muscle cell proliferation and collagen production in the absence of cell toxicity.

PURPOSE: Urinary tract stricture results from excess collagen deposition at an injured area. Paclitaxel (Sigma-Aldrich®) prevents coronary artery restenosis by inhibiting vascular smooth muscle cell proliferation and collagen production. We evaluated the effects of paclitaxel on ureteral smooth muscle cell proliferation and collagen production.

MATERIALS AND

METHODS

Three phases of experiments were done in canine smooth muscle cells. In phase 1 we used proliferation assay to study smooth muscle cells exposed to various concentrations of paclitaxel during 7 days. Phase 2 consisted of 6-day enzyme-linked immunosorbent assay to detect the total amount of type III collagen produced by smooth muscle cells exposed to paclitaxel. In phase 3 we assessed smooth muscle cell membrane damage using a lactate dehydrogenase cytotoxicity assay in which cells were exposed to escalating paclitaxel concentrations for 14 days.

RESULTS

Proliferation studies showed that 10 and 100 nM paclitaxel significantly inhibited ureteral smooth muscle cell proliferation. Enzyme-linked immunosorbent assay revealed significantly decreased type III collagen production at 100 nM. Cytotoxicity testing showed that 1 to 100 nM paclitaxel did not harm smooth muscle cells.

CONCLUSIONS

Paclitaxel effectively inhibits canine ureteral smooth muscle cell proliferation and collagen production without toxicity to smooth muscle cells at concentrations up to 100 nM. These results may ultimately translate into new methods of preventing and treating urinary stricture disease.