RRC ID 62819
著者 Kinashi Y, Ikawa T, Takahashi S.
タイトル The combined effect of neutron irradiation and temozolomide on glioblastoma cell lines with different MGMT and P53 status.
ジャーナル Appl Radiat Isot
Abstract 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.
巻・号 163
ページ 109204
公開日 2020-9-1
DOI 10.1016/j.apradiso.2020.109204
PII S0969-8043(20)30333-X
PMID 32561044
MeSH Antineoplastic Agents, Alkylating / pharmacology* Brain Neoplasms / enzymology Brain Neoplasms / metabolism Brain Neoplasms / pathology* Cell Line, Tumor Combined Modality Therapy DNA Modification Methylases / metabolism* DNA Repair Enzymes / metabolism* Glioblastoma / enzymology Glioblastoma / metabolism Glioblastoma / pathology* Humans Neutrons* Temozolomide / pharmacology* Tumor Suppressor Protein p53 / metabolism* Tumor Suppressor Proteins / metabolism*
IF 1.27
リソース情報
ヒト・動物細胞 T98G(RCB1954) A172(RCB2530)