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Suppression of heat-induced HSF activation by CDDP in human glioblastoma cells
H Matsumoto1, S Hayashi, H Shioura
1Department of Experimental Radiology & Health Physics, Fukui Medical University, Matsuoka, Japan.
Purpose:
The kinetics of the accumulation of inducible 72-kD heat shock protein (hsp72) and the activation of heat shock transcriptional factor (HSF) after hyperthermia and/or CDDP treatment in two human glioblastoma cell lines, A-172 having the wild-type p53 gene and T98G having the mutated p53 gene were evaluated.
Methods And Materials:
Western blot analysis of hsp72, gel-mobility shift assay of HSF, cell survival, and development of thermotolerance were examined.
Results:
The prominent suppression of heat-induced hsp72 accumulation by CDDP was seen in A-172 cells, but not in T98G cells. This was due to the p53-dependent inhibition of heat-induced HSF activation by CDDP. The interactive hyperthermic enhancement of CDDP cytotoxicity was observed in A-172 cells, but not in T98G cells. In addition, the heat-induced thermotolerance was suppressed by the presence of CDDP in the pretreatment.
Conclusion:
Suppression of heat-induced hsp72 accumulation by CDDP contributes to an interactive hyperthermic enhancement of CDDP cytotoxicity in the cells bearing the wild-type p53 gene.