Preferential sensitization of tumor cells to radiation by heat shock protein 90 inhibitor geldanamycin.
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.
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan.
Yoshitaka
Y
Matsumoto
Hikaru
H
Machida
Nobuo
N
Kubota
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D016227:Benzoquinones; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D011809:Quinones / Q000008:administration & dosage*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D016896:Treatment Outcome
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins; D011809:Quinones; D011838:Radiation-Sensitizing Agents; C001277:geldanamycin