Cisplatin, hyperthermia and radiation treatment in human cisplatin-sensitive and resistant glioma cell lines.

In this study, the effects of mild protracted hyperthermia, combined with prolonged exposure to cisplatin and low dose-rate irradiation (LDRI), were examined in two human cell lines. The cell lines are human glioma parental and cisplatin-resistant variant cells. The results show that mild hyperthermia at 40 degrees C was able to sensitize both the parental and the variant cisplatin-resistant cells to cisplatin treatments (1 microgram/ml for up to 20 h) when the two treatments were given concurrently. When mild hyperthermia and cisplatin were given with LDRI concurrently, additional enhanced cell killing was observed in both the parental and the cisplatin-resistant variant cells. Further analysis of the results showed that when the effects of the trimodality treatment were normalized to the effects of the combined treatment of mild hyperthermia with cisplatin, the residual cell killing was still greater than that observed for radiation alone, indicating a synergistic interaction. This synergistic interaction was greater for the parental line compared to the cisplatin-resistant line. Thus, these data show that the concurrent application of mild hyperthermia, low concentration, long duration, cisplatin and low-dose rate irradiation may be an effective form of treatment in both normally responding and cisplatin-resistant variant human tumour cell lines.