At the present time the effective Taxol dose and time-course for the treatment of colonic cancer cells without disruption of normal colonic cell proliferation is not known. The aim of the present study was to determine the effects of Taxol on the growth of normal, polyposis, and cancerous human colonic cells. Cultures of normal human colonic cells, polyposis cells, colon cancer cells (Caco-2, T-84, LoVo cell lines) were plated in multiwell plates. Cell counts or MTT-assay were used to evaluate cell proliferation. Immunofluorescence and Western-blotting measured P- glycoprotein expression. Taxol (1×10-9-1×10-8M) was slightly inhibitory but very inhibitory (>10nM) to normal colonic proliferation. Taxol (1×10-9-1×10-8 M) was effective in the inhibition of polyposis and cancerous cell growth but not at higher doses (1×10-8-1×10-6M). Immunofluorescence and Western- immunoblotting showed a direct relationship between Taxol-induced P-glycoprotein expression and the resistance to Taxol in all cell types. We conclude: 1) lower doses of Taxol are more effective in preventing the growth of colon polyposis and cancer cells with minimal effects on the proliferation of normal colon cells; 2) a direct relationship exists between P-glycoprotein expression and Taxol-drug resistance.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology