Mechanisms of Chemo-Hyperthermic Oncotherapy with Cisplatin in View of Hsp72 Induction.

This is the authors' abstract. We don't add key points for this paper.

Hsp72 is one of the stress proteins induced transcriptionally by various stressors such as heat, UV, ionizing radiation and DNA damaging agents. Many studies have shown a positive relationship between thermosensitivity/thermotolerance and heat shock proteins. On the other hand, cisplatin (cis-diamminedichloroplatinum (II)) is one of the chemotherapeutic agents which are widely effective against human cancers. The cytotoxicity of cisplatin is believed to be due to the formation of DNA adducts, which include mainly inter-and intra-strand DNA crosslinks. Many investigators have shown the cytotoxic effect of cisplatin enhanced by combination with hyperthermia. There are two possible modes of the interaction between hyperthermia and cisplatin. One is an increase of the drug uptake by hyperthermia, which may cause much more DNA damage in cells. The other is that hyperthermia may inhibit the repair of cisplatin-induced DNA damage as is the case in the combination of ionizing radiation and hyperthermia.In the present study, we show the accumulation of hsp72 induced by cisplatin and the suppression of hsp72 accumulation by the combined treatment with hyperthermia and cisplatin, suggesting the third possible mode of interaction between hyperthermia and cisplatin which cisplatin suppresses the heat-induced hsp72 accumulation. These results suggest that the synergistic cytotoxic enhancement by the combination of hyperthermia and cisplatin may be dependent on the suppression of heat-induced hsp72 accumulation by cisplatin.