BACKGROUND AND PURPOSE: 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. MATERIALS AND 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.
BACKGROUND AND PURPOSE: Overexpression of Bcl-2 is frequent in humancancers and has been associated with radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors. MATERIALS AND 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.
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