Growth inhibitory effects of paclitaxel on human epithelioid sarcoma in vitro : Heterogeneity of response and the multidrug resistance phenotype
✍ Scribed by Petra Reinecke; Christiane Knopf; Michael Schmitz; Eva M. Schneider; Helmut E. Gabbert; Claus D. Gerharz
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 321 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
BACKGROUND.
Epithelioid sarcoma is a highly malignant soft tissue tumor that is largely resistant to conventional chemotherapy and radiotherapy. Because paclitaxel has been proven to be effective in other human malignancies refractory to conventional chemotherapy, the authors analyzed the in vitro growth inhibitory effects of paclitaxel on the human epithelioid-sarcoma cell line GRU-1 and its clonal subpopulations GRU-1A, GRU-1B, and GRU-1C.
METHODS.
Paclitaxel-induced morphologic alterations were visualized using light microscopy, immunofluorescence microscopy, and transmission electron microscopy. The antiproliferative effects of paclitaxel on the cell lines were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumЈ bromide (MTT) assay. The extent of paclitaxel-induced apoptosis was determined by light microscopy. The expression and function of P-glycoprotein and the multidrug resistance-associated protein (MRP) were defined by reverse transcriptase-polymerase chain reaction and fluorescence-activated cell sorter analysis.
RESULTS.
Paclitaxel-induced morphologic alterations such as micronucleus formation and microtubule bundles showed no significant differences between the parental cell line and its clonal subpopulations. A significant (P Ͻ 0.05) dosedependent growth inhibition was observed in GRU-1 and its clonal subpopulations, with the IC 50 (concentration that inhibits 50%) values ranging from 0.04-0.49 M in the different subpopulations. Paclitaxel-induced growth inhibition was accompanied by a slight increase in apoptosis. All cell lines showed an expression of and an effective function of P-glycoprotein and MRP.