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The combined effect of neutron irradiation and temozolomide on glioblastoma cell lines with different MGMT and P53 status.
Applied Radiation and Isotopes ( IF 1.6 ) Pub Date : 2020-04-25 , DOI: 10.1016/j.apradiso.2020.109204
Yuko Kinashi 1 , Tomoyuki Ikawa 1 , Sentaro Takahashi 1
Affiliation  

Temozolomide (TMZ) is a DNA-alkylating agent used for chemo-radiotherapy of glioblastoma, which is also a target cancer for boron neutron capture therapy (BNCT). Although the DNA-repair enzyme O6-methylguanine DNA methyltransferase (MGMT) and the tumor suppressor p53 are mutated in some glioblastoma cells, it remains unknown whether these mutations affect sensitivity to neutron irradiation. We examined sensitivity to neutron irradiation and TMZ in two glioblastoma cell lines: T98G, which is p53-mutant with high levels of MGMT activity; and A172, which is p53–wild-type and has low MGMT activity. T98G cells were more resistant to TMZ treatment than A172 cells, with a 10-fold higher LC50. In A172 cells, TMZ treatment did not change the cell-killing effect of neutron irradiation in the presence of borono-phenylalanine (BPA). By contrast, T98G cells were more resistant to neutron irradiation when BPA was present. These results indicate that DNA repair activity in T98G cells might be higher due to upregulation of MGMT after TMZ treatment. Thus, differences in the MGMT and p53 statuses of glioblastoma cells might predict the effect of combination therapy with BNCT and DNA-alkylating agent.



中文翻译:

中子照射和替莫唑胺对具有不同 MGMT 和 P53 状态的胶质母细胞瘤细胞系的联合作用。

替莫唑胺 (TMZ) 是一种 DNA 烷化剂,用于胶质母细胞瘤的放化疗,胶质母细胞瘤也是硼中子俘获疗法 (BNCT) 的靶癌。尽管 DNA 修复酶 O 6-甲基鸟嘌呤 DNA 甲基转移酶 (MGMT) 和肿瘤抑制因子 p53 在一些胶质母细胞瘤细胞中发生突变,但这些突变是否会影响对中子辐射的敏感性尚不清楚。我们检测了两种胶质母细胞瘤细胞系对中子照射和 TMZ 的敏感性:T98G,它是具有高水平 MGMT 活性的 p53 突变体;和 A172,它是 p53 野生型,MGMT 活性低。T98G 细胞比 A172 细胞对 TMZ 处理更具抵抗力,LC50 高 10 倍。在 A172 细胞中,在硼苯丙氨酸 (BPA) 存在下,TMZ 处理不会改变中子照射的细胞杀伤效果。相比之下,当 BPA 存在时,T98G 细胞对中子辐射的抵抗力更强。这些结果表明,由于 TMZ 处理后 MGMT 的上调,T98G 细胞中的 DNA 修复活性可能更高。因此,

更新日期:2020-04-25
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