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論文

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

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

Radiotherapy and Oncology, 89(2), p.231 - 236, 2008/11

 被引用回数:22 パーセンタイル:59.19(Oncology)

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 $$gamma$$-rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution. Whereas Bcl-2 cells were more resistant to $$gamma$$-rays and helium ions (16.2 keV/$$mu$$m) than Neo cells, heavy ions (76.3-1610 keV/$$mu$$m) gave the comparable survival regardless of Bcl-2 overexpression. Carbon ions (108 keV/$$mu$$m) 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. 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.

論文

The Small-molecule Bcl-2 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-ion radiation

浜田 信行*; 片岡 啓子*; 楚良 桜*; 原 孝光*; 大村 素子*; 舟山 知夫; 坂下 哲哉; 中野 隆史*; 小林 泰彦

Radiotherapy and Oncology, 89(2), p.227 - 230, 2008/11

 被引用回数:8 パーセンタイル:31.07(Oncology)

This is the first study to demonstrate that the small-molecule Bcl-2 inhibitor HA14-1 renders human cervical cancer cells and their Bcl-2 over expressing radioresistant counterparts, but not normal fibroblasts, more susceptible to heavy ions. Thus, Bcl-2 may be an attractive target for improving the efficacy of heavy-ion therapy.

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