Influence of induction of HSP70 on the cytotoxicity of oxazaphosphorine compounds and cisplatin

Abstract

Induction of HSP70 and thermotolerance may also decrease the cytotoxicity of cytostatic agents or their combination with hyperthermia in clinically used thermochemotherapy. HSP70 and thermotolerance were induced by hyperthermia (42 degrees C, 1 h) in two human tumor cell lines in vitro and in vivo. The influence of thermotolerance on the cytotoxicity of CDDP and the oxazaphosphorine compounds Mafo and Ifo and their combination with hyperthermia (42 degrees C or 43 degrees C, 1 h) were studied. The results show that neither thermotolerance nor HSP70 affects the tumor cell sensitivity to CDDP or oxazaphosphorine compounds. However, the additive effect of hyperthermia and CDDP was found to be attenuated in thermotolerant cells. The cytotoxicity of oxazaphosphorine compounds combined with hyperthermia was not altered after preheating, suggesting a different mechanism may be responsible for the drug-hyperthermia interaction of CDDP and oxazaphosphorine compounds. There were no differences between in vitro and in vivo results suggesting mechanisms at the cellular level being responsible for the influence of thermotolerance on drug- and drug-hyperthermia action.