Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells.
Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells.
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DOI：
10.1093/jrr/rrv033
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发表时间：
2015-09
影响因子：
2
通讯作者：
Nakano T
中科院分区：
文献类型：
--
作者：
Isono M;Yoshida Y;Takahashi A;Oike T;Shibata A;Kubota Y;Kanai T;Ohno T;Nakano T
碳离子放射治疗(CIRT)在治疗胶质母细胞瘤方面有希望，胶质母细胞瘤是一种侵袭性的X射线抗性脑瘤。然而，由于胶质母细胞瘤细胞表现出高度侵袭性，碳离子(C-ion)照射肿瘤周围正常组织是不可避免的。最近的研究表明，成人大脑中存在神经干细胞。因此，在CIRT的治疗计划中，必须仔细考虑C离子对神经干细胞的损伤作用。在这里，我们研究了人神经干细胞(HNSCs)和胶质母细胞瘤A172细胞在X射线或碳离子束照射后的生长和死亡模式。产生50%增殖率(D50)的X射线剂量，hNSCs为0.8Gy，A172细胞为3.0Gy.碳离子照射后，hNSCs的D50为0.4Gy.A172细胞为1.6Gy.C离子的相对生物学效应值为2.0，A172细胞为1.9.重要的是，X射线和碳离子束都优先诱导hNSCs的凋亡，而不是坏死；然而，辐射诱导的A172细胞的凋亡不那么明显。照射后的hNSCs对凋亡的敏感性与磷酸化P53的持续上调有关，而A172细胞的抗凋亡特性与高基础水平的核因子kappa B表达有关。综上所述，这些数据表明，细胞凋亡是照射后hNSCs的主要死亡途径。神经干细胞对C-离子射线的高度敏感性强调了在胶质母细胞瘤的CIRT治疗计划中仔细描绘靶区体积的重要性。
Carbon-ion radiotherapy (CIRT) holds promise in the treatment of glioblastoma, an aggressive X-ray–resistant brain tumor. However, since glioblastoma cells show a highly invasive nature, carbon-ion (C-ion) irradiation of normal tissues surrounding the tumor is inevitable. Recent studies have revealed the existence of neural stem cells in the adult brain. Therefore, the damaging effect of C-ion beams on the neural stem cells has to be carefully considered in the treatment planning of CIRT. Here, we investigated the growth and death mode of human neural stem cells (hNSCs) and glioblastoma A172 cells after X-ray or C-ion beam irradiation. The X-ray dose resulting in a 50% growth rate (D50) was 0.8 Gy in hNSCs and 3.0 Gy in A172 cells, while the D50 for C-ion beams was 0.4 Gy in hNSCs and 1.6 Gy in A172 cells; the relative biological effectiveness value of C-ion beams was 2.0 in hNSCs and 1.9 in A172 cells. Importantly, both X-rays and C-ion beams preferentially induced apoptosis, not necrosis, in hNSCs; however, radiation-induced apoptosis was less evident in A172 cells. The apoptosis-susceptible nature of the irradiated hNSCs was associated with prolonged upregulation of phosphorylated p53, whereas the apoptosis-resistant nature of A172 cells was associated with a high basal level of nuclear factor kappa B expression. Taken together, these data indicate that apoptosis is the major cell death pathway in hNSCs after irradiation. The high sensitivity of hNSCs to C-ion beams underscores the importance of careful target volume delineation in the treatment planning of CIRT for glioblastoma.