Enhancement of heat-induced heat shock protein (hsp)72 accumulation by doxorubicin (Dox) in vitro

Previous studies have shown that cellular thermotolerance develops in response to exposure to doxorubicin (Dox) and treatment with hyperthermia. In the present study, we evaluated the induction of thermotolerance and the accumulation of heat shock protein (hsp)72 after treatment with Dox and/or hyperthermia at 44°C in Chinese hamster V-79 cells. Thermotolerance developed after exposure to Dox at 37°C for 2 h in a dose-dependent manner. Western blot analysis showed no accumulation of hsp72 after exposure to Dox (0.2 μg/ml) for 2 h (lethal dose (LD)15). Hsp72 accumulated 12 h after hyperthermia at 44°C for 35 min (LD15). However, when the cells were exposed to Dox (0.1 μg/ml) followed by heating at 44°C for 25 min (LD15), accumulation of hsp72 was observed after 6 h. These results suggest that enhancement of induction of hsp72 accumulation by Dox may be involved in the development of thermotolerance induced by sequential treatment with Dox and hyperthermia.