title: Synergistic effect of heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin and X-rays, but not carbon-ion beams, on lethality in human oral squamous cell carcinoma cells.
abstract: The purpose of this study is to clarify the effect of a heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in combination with X-rays or carbon-ion beams on cell killing in human oral squamous cell carcinoma LMF4 cells. Cell survival was measured by colony formation assay. Cell-cycle distribution was analyzed by flow cytometry. Expression of DNA repair-related proteins was investigated by western blotting. The results showed 17-AAG to have synergistic effects on cell lethality with X-rays, but not with carbon-ion beams. The 17-AAG decreased G(2)/M arrest induced by X-rays, but not by carbon-ion beams. Both X-ray and carbon-ion irradiation up-regulated expression of non-homologous end-joining-associated proteins, Ku70 and Ku80, but 17-AAG inhibited only X-ray-induced up-regulation of these proteins. These results show that 17-AAG with X-rays releases G(2)/M phase arrest; cells carrying misrepaired DNA damage then move on to the G(1) phase. We demonstrate, for the first time, that the radiosensitization effect of 17-AAG is not seen with carbon-ion beams because 17-AAG does not affect these changes.
authors: Department of Radiation Oncology,  Gunma University Graduate School of Medicine, Gunma,  Japan.
authors: Atsushi
authors: A
authors: Musha
authors: Yukari
authors: Y
authors: Yoshida
authors: Takeo
authors: T
authors: Takahashi
authors: Koichi
authors: K
authors: Ando
authors: Tomoo
authors: T
authors: Funayama
authors: Yasuhiko
authors: Y
authors: Kobayashi
authors: Akihide
authors: A
authors: Negishi
authors: Satoshi
authors: S
authors: Yokoo
authors: Takashi
authors: T
authors: Nakano
mesh_terms: D016227:Benzoquinones / Q000037:antagonists & inhibitors*; D002244:Carbon / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007477:Ions / Q000627:therapeutic use*; D047029:Lactams, Macrocyclic / Q000037:antagonists & inhibitors*; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D013997:Time Factors; D014965:X-Rays
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D007477:Ions; D047029:Lactams, Macrocyclic; C112765:tanespimycin; D002244:Carbon