Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin.

Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin.
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DOI:
10.1038/srep40588
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发表时间:
2017-01-16
期刊:
影响因子:
4.6
通讯作者:
Nakano T
Nakano T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kobayashi D;Oike T;Shibata A;Niimi A;Kubota Y;Sakai M;Amornwhichet N;Yoshimoto Y;Hagiwara Y;Kimura Y;Hirota Y;Sato H;Isono M;Yoshida Y;Kohno T;Ohno T;Nakano T

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在当今的癌症治疗中,碳离子放射疗法主要用作单一疗法,而顺铂与X射线放射疗法同时使用。碳离子和顺铂联合使用的有效性尚不清楚。为了获得碳离子或X射线和顺铂之间潜在共享的机制的信息,我们评估了敏感性与单一治疗的相关性。在20种人类癌细胞系中,对X射线的敏感性与对顺铂的敏感性密切相关,表明存在潜在的共同靶点机制。有趣的是,对碳离子和顺铂的敏感性的相关性比对X射线和顺铂的敏感性弱得多,表明碳离子和顺铂之间存在潜在的不同靶机制。通过4′,6-diamidino-2-phenylindole dihydrochloride染色评估克隆原性细胞死亡,表明碳离子比相同物理剂量的X射线更有效地诱导有丝分裂灾难,而凋亡和衰老则没有。这些数据表明,对碳离子和顺铂的敏感性的相关性弱于对X射线和顺铂的敏感性,这有助于作为生物学基础来理解这些治疗之间潜在的共同机制。必须进一步研究以阐明碳离子和顺铂组合的临床疗效。
In cancer therapy today, carbon ion radiotherapy is used mainly as monotherapy, whereas cisplatin is used concomitantly with X-ray radiotherapy. The effectiveness of concomitant carbon ions and cisplatin is unclear. To obtain the information on the mechanisms potentially shared between carbon ions or X-rays and cisplatin, we assessed the correlation of sensitivity to the single treatments. In 20 human cancer cell lines, sensitivity to X-rays strongly correlated with sensitivity to cisplatin, indicating the presence of potentially shared target mechanisms. Interestingly, the correlation of sensitivity to carbon ions and cisplatin was much weaker than that of sensitivity to X-rays and cisplatin, indicating the presence of potentially different target mechanisms between carbon ions and cisplatin. Assessment of clonogenic cell death by 4′,6-diamidino-2-phenylindole dihydrochloride staining showed that mitotic catastrophe was more efficiently induced by carbon ions than by the same physical dose of X-rays, while apoptosis and senescence were not. These data indicate that the correlation of sensitivity to carbon ions and cisplatin is weaker than that of sensitivity to X-rays and cisplatin, which are helpful as biological basis to understand the potentially shared mechanism among these treatments. Further investigation is mandatory to elucidate the clinical efficacy of carbon ions and cisplatin combination.