期刊
JOURNAL OF RADIATION RESEARCH
卷 61, 期 6, 页码 832-841出版社
OXFORD UNIV PRESS
DOI: 10.1093/jrr/rraa065
关键词
sensitizing effect; apoptosis; cell cycle; proton therapy; cisplatin; fluorescent ubiquitination-based cell cycle indicator system
资金
- JSPS KAKENHI [15H05675]
- 41th of Aichi Cancer Research Foundation
- 2nd of Kobayashi Foundation for Cancer Research
- Grants-in-Aid for Scientific Research [15H05675] Funding Source: KAKEN
The purpose of the current study was to investigate the biological effects of protons and photons in combination with cisplatin in cultured cells and elucidate the mechanisms responsible for their combined effects. To evaluate the sensitizing effects of cisplatin against X-rays and proton beams in HSG, EMT6 and V79 cells, the combination index, a simple measure for quantifying synergism, was estimated from cell survival curves using software capable of performing the Monte Carlo calculation. Cell death and apoptosis were assessed using live cell fluorescence imaging. HeLa and HSG cells expressing the fluorescent ubiquitination-based cell cycle indicator system (Fucci) were irradiated with X-rays and protons with cisplatin. Red and green fluorescence in the G1 and S/G2/M phases, respectively, were evaluated and changes in the cell cycle were assessed. The sensitizing effects of >= 1.5 mu M cisplatin were observed for both X-ray and proton irradiation (P < 0.05). In the three cell lines, the average combination index was 0.82-1.00 for X-rays and 0.73-0.89 for protons, indicating stronger effects for protons. In time-lapse imaging, apoptosis markedly increased in the groups receiving >= 1.5 mu M cisplatin + protons. The percentage of green S/G2/M phase cells at that time was higher when cisplatin was combined with proton beams than with X-rays (P < 0.05), suggesting more significant G2 arrest. Proton therapy plus >= 1.5 mu M cisplatin is considered to be very effective. When combined with cisplatin, proton therapy appeared to induce greater apoptotic cell death and G2 arrest, which may partly account for the difference observed in the combined effects.
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