Effects of Carbon Ion Beam on Putative Colon Cancer Stem Cells and Its Comparison with X-rays
Effects of Carbon Ion Beam on Putative Colon Cancer Stem Cells and Its Comparison with X-rays
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DOI：
10.1158/0008-5472.can-10-2926
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发表时间：
2011-05-15
期刊：
影响因子：
11.2
通讯作者：
Okayasu, Ryuichi
中科院分区：
文献类型：
--
作者：
Cui, Xing;Oonishi, Kazuhiko;Okayasu, Ryuichi
虽然碳离子治疗设备昂贵，但碳离子束治疗的生物效应可能比光子束的效果更好地对抗癌症（和癌症干细胞）。为了研究碳离子束是否可以通过靶向癌症干细胞样细胞而具有优于X射线的生物学优势，在体外和体内使用了人类结肠癌细胞。在D10值下，碳离子束相对于X射线的体外相对生物学有效性（RBE）值为1.63至1.74。与CD 133（-）、CD 44（-）/ESA（-）细胞相比，CD 133（+）、CD 44（+）/ESA（+）细胞具有更强的集落形成能力、球体形成能力和体内致瘤性。FACS（荧光激活细胞分选）数据显示，在产生相同生物学功效水平的剂量下，用X射线照射后，癌症干细胞样细胞比碳离子更富集。癌症干细胞样细胞的集落测定显示，相对于X射线，碳离子束的D10水平计算的RBE值为2.05至2.28。体内异种移植试验显示RBE为3.05至3.25，根据肿瘤生长抑制的剂量-反应曲线的斜率计算。与30戈伊X射线相比，15戈伊的碳离子照射诱导更严重的异种移植肿瘤细胞空洞化和纤维化，而具有推定的癌症干细胞标记物CD 133、ESA和CD 44的细胞没有显著增强，并且标记物阳性细胞在30戈伊碳离子照射后显著减少。总的来说，碳离子束治疗可能比光子束治疗具有优势，因为它改善了对假定的结肠癌干细胞样细胞的靶向作用。Cancer Res; 71（10）; 3676-87. (C)2011年AACR。
Although carbon ion therapy facilities are expensive, the biological effects of carbon ion beam treatment may be better against cancer (and cancer stem cells) than the effects of a photon beam. To investigate whether a carbon ion beam may have a biological advantage over X-rays by targeting cancer stem-like cells, human colon cancer cells were used in vitro and in vivo. The in vitro relative biological effectiveness (RBE) values of a carbon ion beam relative to X-rays at the D10 values were from 1.63 to 1.74. Cancer stem-like CD133(+), CD44(+)/ESA(+) cells had a greater ability for colony and spheroid formation, as well as in vivo tumorigenicity compared with the CD133(-), CD44(-)/ESA(-) cells. FACS (fluorescence-activated cell sorting) data showed that cancer stem-like cells were more highly enriched after irradiation with X-rays than carbon ion at doses that produced the same level of biological efficacy. A colony assay for cancer stem-like cells showed that RBE values calculated by the D10 levels were from 2.05 to 2.28 for the carbon ion beam relative to X-rays. The in vivo xenotransplant assay showed an RBE of 3.05 to 3.25, calculated from the slope of the dose-response curve for tumor growth suppression. Carbon ion irradiation with 15 Gy induced more severe xenograft tumor cell cavitation and fibrosis without significant enhancement of cells with putative cancer stem cell markers, CD133, ESA, and CD44, compared with 30 Gy X-rays, and marker positive cells were significantly decreased following 30 Gy carbon ion irradiation. Taken together, carbon ion beam therapy may have an advantage over photon beam therapy by improved targeting of putative colon cancer stem-like cells. Cancer Res; 71(10); 3676-87. (C) 2011 AACR.