RRC ID 61948
Author Matsumoto Y, Machida H, Kubota N.
Title Preferential sensitization of tumor cells to radiation by heat shock protein 90 inhibitor geldanamycin.
Journal J Radiat Res
Abstract The purpose of this study was to investigate the radiosensitizing effect of geldanamycin (GA), an inhibitor of heat shock protein 90, on tumour cells and normal cells. We tested the effect of a combination of GA and radiation on cell survival, PI3K/Akt-related proteins and apoptosis induction. GA sensitized tumour cells to radiation in preference to normal cells. In addition, a combination of radiation and GA abolished Akt activities and strongly enhanced the induction of apoptosis in tumour cells which depend on Akt protein activities for cell survival. The present data support the hypothesis that GA sensitizes tumour cells by modulating the balance among mitogenic, antiproliferative and apoptotic pathways. Targeting Hsp90 in tumour cells may lead to the development of new radiosensitizing strategies in radiotherapy.
Volume 46(2)
Pages 215-21
Published 2005-6-1
DOI 10.1269/jrr.46.215
PII JST.JSTAGE/jrr/46.215
PMID 15988140
MeSH Apoptosis / drug effects Apoptosis / radiation effects Benzoquinones Cell Line, Tumor Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Gene Expression Regulation, Neoplastic / drug effects Gene Expression Regulation, Neoplastic / radiation effects HSP90 Heat-Shock Proteins / antagonists & inhibitors* Humans Lactams, Macrocyclic Neoplasm Proteins / metabolism* Neoplasms / pathology Neoplasms / physiopathology* Neoplasms / therapy* Quinones / administration & dosage* Radiation Tolerance / drug effects* Radiation-Sensitizing Agents / administration & dosage* Treatment Outcome
IF 1.95
Resource
Human and Animal Cells NB1RGB(RCB0222)