Sensitization to cisplatin action by step-down heating in cDDP-sensitive and -resistant cells.
Hyperthermia treatment (> or = 43 degrees 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 degrees C), immediately before a treatment at a lower temperature (< 42 degrees 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 degrees C enhanced the cytotoxicity of 41 degrees C hyperthermia alone. It also enhanced sensitivity to cDDP when given at 37 degrees C. However, it did not increase the 41 degrees 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 degrees 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 degrees 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.
Hettinga
J V
JV
Department of Radiobiology, University of Groningen, The Netherlands.
Lemstra
W
W
De Vries
E G
EG
Konings
A W
AW
Kampinga
H H
HH
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D002945:Cisplatin