Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France.
Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France; Départment de Radiothérapie, Institut de Cancérologie Lucien Neuwirth, 42271 St Priest-en-Jarez, France.
Cancer Lett. 2015 Apr 28;360(1):10-6. doi: 10.1016/j.canlet.2015.01.025. Epub 2015 Feb 2.
This study aimed to examine the cellular and molecular long-term responses of glioblastomas to radiotherapy and hadrontherapy in order to better understand the biological effects of carbon beams in cancer treatment. Eleven human glioblastoma cell lines, displaying gradual radiosensitivity, were irradiated with photons or carbon ions. Independently of p53 or O(6)-methylguanine-DNA methyltransferase(1) status, all cell lines responded to irradiation by a G2/M phase arrest followed by the appearance of mitotic catastrophe, which was concluded by a ceramide-dependent-apoptotic cell death. Statistical analysis demonstrated that: (i) the SF2(2) and the D10(3) values for photon are correlated with that obtained in response to carbon ions; (ii) regardless of the p53, MGMT status, and radiosensitivity, the release of ceramide is associated with the induction of late apoptosis; and (iii) the appearance of polyploid cells after photon irradiation could predict the Relative Biological Efficiency(4) to carbon ions. This large collection of data should increase our knowledge in glioblastoma radiobiology in order to better understand, and to later individualize, appropriate radiotherapy treatment for patients who are good candidates.
本研究旨在研究脑胶质瘤对放射治疗和强子治疗的细胞和分子的长期反应，以便更好地了解碳束在癌症治疗中的生物学效应。选择 11 个人类脑胶质瘤细胞系，这些细胞系对放射的敏感性逐渐增加，用光子或碳离子照射。独立于 p53 或 O(6)-甲基鸟嘌呤-DNA 甲基转移酶(1)的状态，所有细胞系对照射的反应均为 G2/M 期阻滞，随后出现有丝分裂灾难，最终通过依赖神经酰胺的凋亡细胞死亡来结束。统计分析表明：(i) 光子的 SF2(2)和 D10(3)值与碳离子的反应相关；(ii) 无论 p53、MGMT 状态和放射敏感性如何，神经酰胺的释放与晚期凋亡的诱导有关；(iii) 光子照射后出现的多倍体细胞可以预测对碳离子的相对生物效率(4)。本大量数据集应该增加我们对脑胶质瘤放射生物学的认识，以便更好地理解，并随后为合适的放射治疗个体化治疗合适的患者。
