Paclitaxel inhibits proliferation of cell lines responsible for metal stent obstruction: possible topical application in malignant bile duct obstructions.

RATIONALE AND
OBJECTIVES: To evaluate a dose dependent inhibitory effect of paclitaxel to assess a possible local application for biliary tract malignancies in conjunction with stent placement.
METHODS: Cell cultures of the three different cell types (human epithelial gallbladder cells [HEGC], human fibroblasts [HF; PA 314 wt] and pancreatic carcinoma cells [PC; P181]) were incubated for 20 minutes at 37 degrees C with increasing doses of paclitaxel (1.0 x 10(-4) - 1.0 x 10(2) micromol). Half of the cultures were then incubated without paclitaxel, the other half with paclitaxel for 20 minutes, 24 hours, or 72 hours. Cell proliferation was detected by photometric measurements of mitochondrial dehydrogenase activity (MTT assay).
RESULTS: Incubation of cell cultures with paclitaxel resulted in a dose dependent and cell specific inhibition of cell proliferation. Concentrations of 1.0 x 10(-4) (and higher) paclitaxel for 20 minutes resulted in a inhibition of cell proliferation of HEGC (28%), PA (26%), and HF (17%). A prolonged paclitaxel incubation (up to 72 hours) resulted in an inhibitory effect on cell proliferation of HEGC (40%), PA (45%), and HF (39%). Cytotoxic effects, manifested by development of vacuoles and damage of cell integrity were seen at concentrations above 1.0 x 10(1) for both the short and long term incubation.
CONCLUSIONS: Paclitaxel incubation resulted in a dose dependent inhibition of cell proliferation of human epithelial gallbladder cells, human fibroblasts and pancreatic carcinoma cells. This inhibitory effect of paclitaxel on the cell lines could serve as the basis to develop drug coated or drug eluting stents for malignant biliary strictures.