Growth Inhibitory Effects Of Paclitaxel (Taxol (R)) On Human Epithelioid Sarcomas In Vitro: Heterogeneity Of Response And The Multidrug Resistance Phenotype

Epithelioid sarcoma is a highly malignant soft-tissue tumor, which is largely resistant to conventional chemotherapy and radiotherapy. Therefore, we analyzed the in vitro growth-inhibitory effects of paclitaxel on the human epithelioid-sarcoma cell line GRU-1 and its clonal subpopulations with a maximal reduction of cell viability down to 1% of the control after exposure to 10 mu M paclitaxel (Taxol(R)). The paclitaxel (Taxol(R)) concentrations required for a 50 % inhibition of growth (IC50) ranged from 0.04 mu M to 0.49 mu M in the different subpopulations. Paclitaxel (Taxol(R))-induced morphological alterations such as micronucleus formation and microtubule bundles showed no significant differences between the parental cell line and its clonal subpopulations. The response of GRU-1 and its clonal subpopulations to paclitaxel (Taxol(R)) could not be predicted by the expression and function of P-glycoprotein and Multidrug Resistance associated Protein (MRP), as revealed by RT-PCR, FACScan and the Rh 123 efflux assay. In conclusion, paclitaxel (Taxol(R)) can effectively inhibit the growth of some epithelioid sarcoma subpopulations in vitro, although the extent of response could not directly be related to the multidrug resistance phenotype.