重离子对神经胶质瘤肿瘤干细胞的杀伤及其机理研究

发布时间：2018-05-11 21:17

本文选题：碳重离子 + X射线　；参考：《中国科学院大学(中国科学院近代物理研究所)》2017年博士论文

【摘要】：虽然重离子束治癌已经被证明有着射程岐离和横向散射小、入口坪区能量释放小、相对生物学效应高等显著优点,但重离子辐照对肿瘤干细胞所产生的辐射生物学效应特性依旧不明确。本论文使用了两种人源的神经胶质瘤肿瘤干细胞模型和人工诱导的荷瘤小鼠模型,从体内和体外两个层面来研究在面对神经胶质瘤肿瘤干细胞时,重离子相对于传统X射线是否有明显的生物学优势,并进行机理初探。体外实验结果显示,相对于X射线,相同剂量的碳离子辐照使肿瘤干细胞的DNA损伤的修复率更低;碳离子辐照引起的肿瘤干细胞DNA不稳定性更严重;碳离子辐照处理后肿瘤干细胞的活力更低,说明碳离子对神经胶质瘤肿瘤干细胞的直接杀灭效果要好于X射线。小鼠活体实验显示,碳离子辐照和X射线辐照相比能更好的杀伤小鼠脑中的神经胶质瘤,且能显著降低小鼠脑中瘤区内的神经胶质瘤干性细胞的比例。最后,本论文通过检测长链非编码RNA(LncRNA)的表达和功能,初步探讨了重离子对肿瘤干细胞杀伤效应的机理。实验结果显示,神经胶质瘤肿瘤干细胞中#13、#23或#33 LncRNA的稳态变化会导致细胞内p53上调,最终导致细胞走向凋亡或坏死。综上所述,碳离子和传统X射线相比,无论是在神经胶质瘤肿瘤干细胞的体外细胞实验中,还是在小鼠脑部神经胶质瘤的体内实验中,都有着明显的生物学优势,而在整个过程中,LncRNA可能发挥着非常重要的作用。这些发现对于更好的理解重离子束治癌相关的生物学效应上有重要作用。
[Abstract]:Although the treatment of cancer by heavy ion beam has been proved to have the advantages of low range divergence and transverse scattering, small energy release from the entrance plateau, and higher biological effect, However, the radiobiological effects of heavy ion irradiation on tumor stem cells are still unclear. In this paper, two kinds of human glioma tumor stem cell models and artificially induced tumor bearing mice models were used to study the human glioma tumor stem cells in vivo and in vitro. Whether heavy ions have obvious biological advantages over conventional X-rays and its mechanism are discussed. The results of in vitro experiments showed that the repair rate of DNA damage of tumor stem cells was lower than that of X-ray irradiation, and the DNA instability of tumor stem cells induced by carbon ion irradiation was more serious. The activity of tumor stem cells treated with carbon ions was lower than that of X-ray irradiation, which indicated that the direct killing effect of carbon ions on glioma tumor stem cells was better than that on X-ray. In vivo experiments in mice showed that carbon ion irradiation could kill glioma more effectively than X ray irradiation, and could significantly reduce the proportion of dry glioma cells in the tumor area of mouse brain. Finally, the mechanism of killing effect of heavy ions on tumor stem cells was studied by detecting the expression and function of long chain noncoding RNAs (LncRNAs). The results showed that the steady-state changes of #13C #23 or #33 LncRNA in glioma stem cells resulted in up-regulation of p53 and eventually apoptosis or necrosis of the cells. In conclusion, compared with conventional X-ray, carbon ions have obvious biological advantages in both in vitro cell experiments of glioma tumor stem cells and in vivo experiments of mouse brain gliomas. LncRNA may play a very important role in the whole process. These findings are important for a better understanding of the biological effects associated with heavy ion beam therapy.
【学位授予单位】：中国科学院大学(中国科学院近代物理研究所)
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R739.41

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