CREMOPHOR-EL ENHANCES TAXOL EFFICACY IN A MULTIDRUG RESISTANT C1300 NEUROBLASTOMA CELL-LINE

We have previously developed a homoharringtonine (HHT) resistant murin e C1300 neuroblastoma cell line with increased p-glycoprotein expressi on and cross resistance to Adriamycin. Drug resistance in this cell li ne was reversed using cyclosporin-A, dipyridamole and cremophor-EL (CR E). Because of the high CRE content of parenteral taxol, we examined t he ability of this solvent to reverse taxol cross-resistance in this c ell line. Comparative ID-50s using clonogenic assays in agar indicate a 214-fold resistance to HHT. CRE reverses taxol cross-resistance in a dose-dependent manner from 0.003 to 0.1%, and is maximally effective at a subtoxic concentration of 0.03%. High pressure liquid chromatogra phy (HPLC) analysis of taxol treated C1300/HHT cells reveal that CRE c auses changes in intracellular drug levels that are not related to dru g efflux. Our work shows that clinical preparations of taxol, when dil uted to effective doses, contain enough CRE to mitigate multi-drug res istance. Clinical successes of taxol in refractory tumors may be due i n part to the ability of its CRE base to reverse multi-drug resistance .