| Abstract: | Hyperthermia treatment (≥ 43°C) has been shown to be able to (partially) reverse acquired cDDP resistance. However, such heat treatment is difficult to achieve in the clinic. Short pre-treatment at a high temperature (>42°C), immediately before a treatment at a lower temperature (<42°C) can enhance the heat toxicity of the lower temperatures. This “step-down heating schedule” was explored for its possible drug-sensitizing potential in in vitro-cultured cDDP-sensitive and -resistant murine and human tumour cells. A 10-min pre-treatment at 44°C enhanced the cytotoxicity of 41°C hyperthermia alone. It also enhanced sensitivity to cDDP when given at 37°C. However, it did not increase the 41°C-induced cDDP sensitization. Thus, no correlation was found between heat kill and cDDP sensitization for step-down heating schedules. The observed effects of step-down heating were comparable in sensitive and in resistant cells, so the step-down heating schedule, unlike the 43°C treatment, did not lead to a decrease of the cDDP-resistance factor. Yet the total cytotoxicity caused by this treatment protocol was 10-fold more than for cDDP with 41°C alone, due to the extra hyperthermic cell killing and the cDDP-sensitizing effect of the pre-treatment. This treatment could have a substantial impact on cDDP efficacy in the clinic even when cDDP resistance has developed. © 1995 Wiley-Liss, Inc. |
