Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2.
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.
Hamada
Nobuyuki
N
Department of Quantum Biology, Gunma University Graduate School of Medicine, Gunma, Japan. hamada@med.gunma-u.ac.jp
Hara
Takamitsu
T
Omura-Minamisawa
Motoko
M
Funayama
Tomoo
T
Sakashita
Tetsuya
T
Sora
Sakura
S
Yokota
Yuichiro
Y
Nakano
Takashi
T
Kobayashi
Yasuhiko
Y
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*
D019253:Proto-Oncogene Proteins c-bcl-2; D002244:Carbon