Takahashi Momoko, Hirakawa Hirokazu, Yajima Hirohiko, Izumi-Nakajima Nakako, Okayasu Ryuichi, Fujimori Akira
Translational Research Center, Fukushima Medical University , Fukushima.
Int J Radiat Biol. 2014 Dec;90(12):1125-32. doi: 10.3109/09553002.2014.927933. Epub 2014 Aug 11.
To obtain human glioblastoma cells A172 expressing stem cell-related protein and comparison of radiosensitivity in these cells with X-rays and carbon beam.
Human monolayer-type A172 glioblastoma cells were maintained in normal medium with 10% bovine serum. In order to obtain sphere-type A172 cells the medium was replaced with serum-free medium supplemented with growth factors. Both types of A172 cells were irradiated with either X-rays or carbon ion beams and their radiosensitivity was evaluated.
Serum-free medium induced expression of stem cell-related proteins in A172 cells along with the neurosphere-like appearance. These sphere-type cells were found resistant to both X-rays and carbon ion beams. Phosphorylation of histone H2A family member X persisted for a longer period in the cells exposed to carbon ion beams than in those exposed to X-rays and it disappeared quicker in the sphere type than in the monolayer type. Relative radioresistance of the sphere type cells was smaller for carbon ion beams than for X-rays.
We demonstrated that glioblastoma A172 cells with induced stem cell-related proteins turned resistant to irradiation. Accelerated heavy ion particles may have advantage over X-rays in overcoming the tumor resistance due to cell stemness.
获得表达干细胞相关蛋白的人胶质母细胞瘤A172细胞,并比较这些细胞对X射线和碳离子束的放射敏感性。
人单层型A172胶质母细胞瘤细胞在含10%牛血清的正常培养基中培养。为了获得球形A172细胞,将培养基换成添加生长因子的无血清培养基。两种类型 的A172细胞均用X射线或碳离子束照射,并评估其放射敏感性。
无血清培养基诱导A172细胞中干细胞相关蛋白的表达,并呈现神经球样外观。发现这些球形细胞对X射线和碳离子束均具有抗性。与暴露于X射线的细胞相比,暴露于碳离子束的细胞中组蛋白H2A家族成员X的磷酸化持续时间更长,并且在球形细胞中比在单层细胞中消失得更快。球形细胞对碳离子束的相对放射抗性比对X射线的小。
我们证明,诱导表达干细胞相关蛋白的胶质母细胞瘤A172细胞对辐射产生抗性。在克服由于细胞干性导致的肿瘤抗性方面,加速重离子粒子可能比X射线具有优势。