Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2

Bcl-2過剰発現腫瘍の放射線抵抗性は重粒子線照射により消失する

浜田 信行*; 原 孝光*; 大村 素子*; 舟山 知夫; 坂下 哲哉; 楚良 桜; 横田 裕一郎; 中野 隆史*; 小林 泰彦

Hamada, Nobuyuki*; Hara, Takamitsu*; Omura, Motoko*; Funayama, Tomoo; Sakashita, Tetsuya; Sora, Sakura; Yokota, Yuichiro; Nakano, Takashi*; Kobayashi, Yasuhiko

Overexpression of Bcl-2 is frequent in human cancers and has been associated with the radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors. Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) exposed to -rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution. Whereas Bcl-2 cells were more resistant to -rays and helium ions (16.2 keV/m) than Neo cells, heavy ions (76.3-1610 keV/m) gave the comparable survival regardless of Bcl-2 overexpression. Carbon ions (108 keV/m) decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells, and prolonged G/M arrest that occurred more extensively in Bcl-2 cells than in Neo cells. 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/M arrest. Thus, heavy-ion therapy may be a promising modality for Bcl-2 overexpressing radioresistant tumors.