title: Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2.
abstract: OBJECTIVE
  Overexpression of Bcl-2 is frequent in human cancers and has been associated with radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors.
  
  
  METHODS
  Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) exposed to gamma-rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution.
  
  
  RESULTS
  Whereas Bcl-2 cells were more resistant to gamma-rays (0.2keV/microm) and helium ions (16.2keV/microm) than Neo cells, heavy ions (76.3-1610keV/microm) yielded similar survival regardless of Bcl-2 overexpression. Carbon ions (108keV/microm) decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells, and prolonged G(2)/M arrest that occurred more extensively in Bcl-2 cells than in Neo cells.
  
  
  CONCLUSIONS
  High-LET heavy ions overcome tumor radioresistance caused by Bcl-2 overexpression, which may be explained at least in part by the enhanced apoptotic response and prolonged G(2)/M arrest. Thus, heavy-ion therapy may be a promising modality for Bcl-2 overexpressing radioresistant tumors.
authors.affiliation: Department of Quantum Biology, Gunma University Graduate School of Medicine, Gunma, Japan. hamada@med.gunma-u.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamada
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Hara
authors.forename: Motoko
authors.initials: M
authors.lastname: Omura-Minamisawa
authors.forename: Tomoo
authors.initials: T
authors.lastname: Funayama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sakashita
authors.forename: Sakura
authors.initials: S
authors.lastname: Sora
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yokota
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D002244:Carbon; D016923:Cell Death / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D006367:HeLa Cells / Q000378:metabolism / Q000528:radiation effects; D020450:Heavy Ions; D006801:Humans; D018499:Linear Energy Transfer; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D002244:Carbon