Suppression of heat-induced hsp72 accumulation by cisplatin in human glioblastoma cells

The accumulation of the inducible hsp72 (72-kDa heat shock protein) after hyperthermia and/or cisplatin treatment in human glioblastoma cell line (A-172) was studied by Western blot analysis. The level of hsp72 increased to eight-fold 10 h after hyperthermia alone (44 degrees C for 20 min, D-50) and to three-fold 10 h after cisplatin treatment (5 mu g/ml) at 37 degrees C for 15 min (D-50). In contrast, when the cells were simultaneously heated with cisplatin, the accumulation of hsp72 was suppressed. The level of hsp72 increased to about six-fold and two-fold 10 h after hyperthermia (44 degrees C, 15 min) in the presence of 1 and 10 mu g/ml (D-50 or D-10) of cisplatin, respectively. In addition, we found both the enhancement of thermosensitivity and the suppression of thermotolerance by the simultaneously combined treatment of hyperthermia and cisplatin. It has been reported that the enhancement of cisplatin cytotoxicity by hyperthermia is due to increase of both cisplatin uptake and DNA damage by hyperthermia. Our results suggest that the interactive cytotoxic enhancement by the combination of hyperthermia and cisplatin may be also due to the suppression of heat-induced hsp72 accumulation by cisplatin.