Effects of paclitaxel on the growth of normal, polyposis, and cancerous human colonic epithelial cells

BACKGROUND, The specific paclitaxel dose or time course in the treatment of colon carcinoma without the disruption of normal colonic cell proliferatio n is currently not known. The aim of this study was to determine the effect s of paclitaxel on the growth of human colonic epithelial cells using cultu res of normal, polyposis, and cancerous cells. METHODS, Normal, polyposis, and cancerous human colonic cells (Caco-2, T-84 , and LoVo cell lines) were cultured, then treated with paclitaxel (10(-9)- 10(-5) M) for 0-7 days. {AU: Please verify all dosages throughout.} Cell pr oliferation was assayed using either a Coulter-Counter or MTT-growth assay. Immunofluorescence and Western immunoblotting measured P-glycoprotein. RESULTS. Low paclitaxel doses (1 x 10(-9)-10(-8) M) were more effective tha n higher paclitaxel doses (>1 x 10(-8) M) in the growth inhibition of polyp osis, Caco-2, and LoVo cancer (but not T-84) cell lines. Low paclitaxel dos es had little effect on normal colonic cell growth over 7 days. Higher pacl itaxel doses (>1 x 10(-8)-10(-5) M) produced a dose-dependent inhibitory ef fect on the growth of normal human colonic epithelial cells over 7 days but had no effect on the growth of polyposis, Caco-2, and LoVo cells over 3-7 days of treatment. Immunofluorescence and Western immunoblotting of culture s showed that 1 x 10(-6) M paclitaxel increased P-glycoprotein expression i n Caco-2 and LoVo cells. There was no effect of paclitaxel on P-glycoprotei n expression in T-84 cancer cells, which were found to have high endogenous basal levels of P-glycoprotein. P-glycoprotein expression in Caco-2 cells was found on plasma membranes and in perinuclear areas. CONCLUSIONS. Lower paclitaxel doses are more effective over time for the gr owth inhibition of polyposis and cancerous colonic cells, with minimal effe cts on the growth of normal colonic epithelial cells. Increased P-glycoprot ein expression appears to be correlated with paclitaxel resistance in polyp osis and cancerous colonic cells. (C) 1999 American Cancer Society.