Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells
Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells
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DOI：
10.1016/j.radonc.2012.08.009
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发表时间：
2012-11-01
影响因子：
5.7
通讯作者：
Kamada, Tadashi
中科院分区：
文献类型：
--
作者：
Oonishi, Kazuhiko;Cui, Xing;Kamada, Tadashi
目的：从克隆形成存活和DNA修复的角度研究了碳离子束和X射线对人胰腺癌干细胞样细胞的影响。材料和方法：用和不用碳离子和X射线照射人胰腺癌干细胞样细胞，然后进行集落、球体和肿瘤形成测定以及γ H2 AX灶形成测定。对于MIA PaCa-2和BxPc-3细胞，碳离子束相对于X射线在D10值的相对生物学有效性（RBE）值为1.85-2.10。癌干细胞样CD 44（+）/CD 24（+）细胞的集落、球状体形成和致瘤能力明显高于非癌干细胞样CD 44（-）/CD 24（-）细胞。流式细胞仪数据显示，与等有效剂量的碳离子照射相比，X射线照射后CD 44（+）/CD 24（+）细胞的富集程度更高。对于CD 44（+）/CD 24（+）细胞，在D10水平，碳离子束相对于X射线的RBE值为2.0-2.19。经X射线或碳离子束照射后，CD 44（-）/CD 24（-）细胞γ H2 AX灶的数量均高于CD 44（+）/CD 24（+）细胞。结论：碳离子束对胰腺癌干细胞样细胞具有上级杀伤作用，延长DNA损伤时间可能是其放射生物学效应高于X射线的重要机制之一。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。放射治疗和肿瘤学105（2012）258-265
Purpose: The effects of a carbon ion beam and X-rays on human pancreatic cancer stem-like cells were examined from the point of view of clonogenic survival and DNA repair.Materials and methods: Human pancreatic cancer stem-like cells were treated with and without carbon ion and X-ray irradiation, and then colony, spheroid and tumor formation assays as well as gamma H2AX foci formation assay were performed.Results: The relative biological effectiveness (RBE) values of a carbon ion beam relative to X-ray for the MIA PaCa-2 and BxPc-3 cells at the D10 values were 1.85-2.10. The ability for colony, spheroid formation, and tumorigenicity from cancer stem-like CD44(+)/CD24(+) cells is significantly higher than that from non-cancer stem-like CD44(-)/CD24(-) cells. FACS data showed that CD44(+)/CD24(+) cells were more highly enriched after X-rays compared to carbon ion irradiation at isoeffective doses. The RBE values for the carbon ion beam relative to X-ray at the D10 levels for CD44(+)/CD24(+) cells were 2.0-2.19. The number of gamma H2AX foci in CD44(-)/CD24(-) cells was higher than that of CD44(+)/CD24(+) cells after irradiation with either X-ray or carbon ion beam. The number of gamma H2AX foci in CD44(+)/CD24(+) cells was almost the same in the early time, but it persists significantly longer in carbon ion beam irradiated cells compared to X-rays.Conclusions: Carbon ion beam has superior potential to kill pancreatic cancer stem cell-like cells, and prolonged induction of DNA damage might be one of the pivotal mechanisms of its high radiobiological effects compared to X-rays. (C) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 105 (2012) 258-265