Multiple drug-resistant C6 glioma cells cross-resistant to irradiation

Although many advances in antineoplastic therapy have taken place, a clinical breakthrough in the therapy of malignant gliomas is still required. One of the reasons for this is the poor response to cytotoxic drugs and irradiation. We established a subline of the rat glioma cell line C6, named C6,5 x 10(-7) Dox, by exposure to increasing doses of doxorubicin for 5 months. C6,5 x 10(-7) Dox cells expressed high levels of P-glycoprotein (Pgp), known to function as an energy-dependent efflux pump for lipophilic drugs causing the multidrug resistance phenotype. Pgp, which normally has a molecular weight of 170 to 180 kd, appears in C6,5 x 10(-7) Dox cells as two bands with a molecular weight of 140 and 120 kd in western blots. In addition to the typical cross-resistance to doxorubicin, daunorubicin, vincristine and etoposide, we observed a significant resistance of the C6,5 x 10(-7) Dox cell line to irradiation, which cannot be explained by Pgp-expression.