Sensitization of C6 glioma to carboplatin cytotoxicity by hyperthermia and thymidine

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Abstract
Thymidine (a nucleoside metabolite) and 41.8° C hyperthermia were used to sensitize C6 glioma cells to carboplatin cytotoxicity in vitro. Clinically achievable thymidine concentrations (0, 200, 400, or 1000 µg/ml × 24 hours) significantly enhanced carboplatin killing. Clinically achievable hyperthermia exposures (40.5 or 41.8° C x 1 hour) also enhanced carboplatin killing; 41.8° C was more effective than was 40.5° C. Thymidine and 41.8°C hyperthermia together enhanced carboplatin killing significantly more than did the thymidine-carboplatin or hyperthermia-carboplatin combinations. These results illustrate the concept of ‘combination chemosensitization’ for simultaneously addressing the divergent drug resistance mechanisms of malignant gliomas.