CYTOTOXICITY OF TAXOL IN-VITRO AGAINST HUMAN AND RAT MALIGNANT BRAIN-TUMORS

Taxol is a novel antitumor alkaloid that has shown clinical activity against several tumors, including ovarian and breast carcinoma and melanoma. To evaluate taxol's potential as a therapy for malignant brain tumors, we measured the sensitivity of four human (U87, U373, H80, and D324) and two rat (9L, F98) brain-tumor cell lines to taxol. The cells were exposed to taxol in vitro using a clonogenic assay. Log cell kill (LD(90)) occurred at concentrations of 42 (9L), 25 (F98), 19 (H80), 7.2 (U373), 9.1 (U87), and 3.9 nM (D324) when cells were continuously exposed to taxol for 6-8 days. The human cell lines were uniformly more sensitive to taxol than were the rat lines. The duration of exposure had a significant effect on taxol's cytotoxicity. When cells were exposed to taxol for 1 h the LD(90) increased to 890 nM for the 9L rat line and 280 nM for the human U373 line. On the basis of these results, we conclude that taxol has significant potency in vitro against malignant brain tumors and that the activity occurs at concentrations of taxol that have previously been shown to be effective for several tumors against which the drug is currently being evaluated clinically.