ABSTRACT 2446(P14)
ヒト神経膠芽腫細胞におけるシスプラチン/温熱同時併用処理によるp53依存性HSF活性化抑制:小久保菜穂子1,松本英樹1,林 幸子1,畑下昌範1,塩浦宏樹2,大坪俊雄3,北井隆平4,加納永一1(福井医大・1放基,3耳,4脳外,2市立泉佐野病院・放)
p53-dependent suppression of heat-induced HSF activation by CDDP in human glioblastoma cells.: Nahoko KOKUBO1, Hideki MATSUMOTO1, Sachiko HAYASHI1, Masanori HATASHITA1, Hiroki SHIOURA2, Toshio OHTSUBO3, Ryuhei KITAI4 and Eiichi KANO1 (1Depts. of Exptl' Radiol., 3Otorhinolaryngol., 4Neurosurg., Fukui Med. Univ., 2Div. Radiol., Izumisano Hosp.)
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 pre-treatment.
Conclusion: Suppression of heat-induced hsp72 accumulation by CDDP and an interactive thermal chemoenhancement were observed only in the cells bearing the wild-type p53 gene, suggesting enhancement in the cellular thermosensitivity.