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.
Denecke
J
J
University Hospital of Münster, Department of Pediatric Oncology, Germany.
Fiedler
K
K
Hacker-Klom
U
U
Mölenkamp
G
G
Jürgens
H
H
Wolff
J E
JE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D003630:Daunorubicin / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity*; D018432:Drug Resistance, Multiple; D005047:Etoposide / Q000633:toxicity; D005910:Glioma; D011836:Radiation Tolerance; D051381:Rats; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003037:Cobalt Radioisotopes; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D014700:Verapamil; D003630:Daunorubicin