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首页> 美国卫生研究院文献>Journal of Radiation Research >Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells
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Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells

机译：与胶质母细胞瘤A172细胞相比碳离子束可有效诱导人神经干细胞的生长抑制和凋亡

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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.
机译：碳离子放射疗法（CIRT）在胶质母细胞瘤（一种侵袭性X射线耐药的脑肿瘤）的治疗中具有广阔的前景。但是，由于胶质母细胞瘤细胞表现出高度侵袭性，因此不可避免地需要对肿瘤周围的正常组织进行碳离子（C-离子）照射。最近的研究表明，成年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离子束对神经干细胞的破坏作用。在这里，我们研究了人类神经干细胞（hNSCs）和胶质母细胞瘤A172细胞在X射线或C离子束照射后的生长和死亡模式。导致50％的生长率（D50）的X射线剂量在hNSCs中为0.8 Gy，在A172细胞中为3.0 Gy，而在hNSCs中C离子束的D50为0.4 Gy，在A172细胞中为1.6 Gy。 C离子束的相对生物有效性值在hNSC中为2.0，在A172细胞中为1.9。重要的是，X射线和C离子束都优先诱导hNSC中的细胞凋亡，而不是坏死。然而，辐射诱导的细胞凋亡在A172细胞中不太明显。辐射的hNSCs的凋亡易感性与磷酸化p53的长期上调有关，而A172细胞的抗凋亡性与高水平的核因子κB基础表达有关。综上所述，这些数据表明凋亡是辐射后hNSC中主要的细胞死亡途径。 hNSC对C离子束的高度敏感性突出了在胶质母细胞瘤CIRT的治疗计划中仔细确定目标体积的重要性。

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