Effects of combined treatment with 40 degrees C hyperthermia and bleomycin on the accumulation of heat shock protein in murine L cells.
Our research group has reported the enhanced cytotoxicity of combined treatment with bleomycin (BLM) and low hyperthermia at 40 degrees C, using murine L cells, and suggested that post-heating could inhibit BLM-induced sublethal damage repair. For further understanding of the involved mechanisms, we subsequently investigated the kinetics of the cellular accumulations of inducible 72-kDa heat shock protein (hsp72) after 40 degrees C hyperthermia and/or BLM treatment using the same cell line. Western blot analysis showed significantly enhanced accumulation of hsp72 after a low hyperthermia at 40 degrees C for 40, 105 or 180 min, and no significant enhancement of it after exposure to 10 microg/ml BLM at 37 degrees C for either 40 or 105 min. When the cells were heated in the presence of BLM, the accumulations of hsp72 were markedly suppressed, with the maxima of hsp72 accumulation decreasing to 38% and 63% of those induced by hyperthermia alone for 40 or 105 min, respectively. On the other hand, sequential treatment with hyperthermia either before or after BLM treatment did not show significant alteration of the heat-induced accumulations of hsp72. It was demonstrated that BLM was necessary during heating to effectively suppress the heat-induced accumulation of hsp72. This study indicates that the suppression of heat-induced accumulation of hsp72 by BLM may partially contribute to enhance cytotoxicity of the simultaneous treatment of 40 degrees C hyperthermia and BLM.
Jin
Zhao-Hui
ZH
Department of Experimental Radiology and Health Physics, Fukui Medical University, Matsuoka, Fukui 910-1193, Japan.
Shioura
Hiroki
H
Kano
Eiichi
E
Hayashi
Sachiko
S
Hatashita
Masanori
M
Matsumoto
Hideki
H
Ohtsubo
Toshio
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D003131:Combined Modality Therapy; D005347:Fibroblasts / Q000187:drug effects*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006979:Hyperthermia, Induced; D007739:L Cells; D051379:Mice; D008809:Mice, Inbred C3H; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D001761:Bleomycin