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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 696 - 705 (10page)
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초록· 키워드
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Purpose Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. Materials and Methods Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distribution were assayed by western blot for cleaved caspase-3, H2AX staining, and flow cytometry, respectively. Results DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. Conclusion Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.
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등록된 정보가 없습니다.
참고문헌 (30)
참고문헌 신청
Stupp R / 2009 / Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study : 5-year analysis of the EORTC-NCIC trial / Lancet Oncol 10:459~466
Mirimanoff RO / 2006 / Radiotherapy and temozolomide for newly diagnosed glioblastoma : recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial / J Clin Oncol 24:2563~2569
Hegi ME / 2005 / MGMT gene silencing and benefit from temozolomide in glioblastoma / N Engl J Med 352:997~1003
Costello JF / 1994 / Graded methylation in the promoter and body of the O6-methylguanine DNA methyltransferase(MGMT)gene correlates with MGMT expression in human glioma cells / J Biol Chem 269:17228~17237
Wee CW / 2017 / Novel recursive partitioning analysis classification for newly diagnosed glioblastoma : a multi-institutional study highlighting the MGMT promoter methylation and IDH1 gene mutation status / Radiother Oncol 123:106~111
Mirimanoff RO / 2006 / Radiotherapy and temozolomide for newly diagnosed glioblastoma : recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial / J Clin Oncol 24:2563~2569
Hegi ME / 2005 / MGMT gene silencing and benefit from temozolomide in glioblastoma / N Engl J Med 352:997~1003
Costello JF / 1994 / Graded methylation in the promoter and body of the O6-methylguanine DNA methyltransferase(MGMT)gene correlates with MGMT expression in human glioma cells / J Biol Chem 269:17228~17237
Wee CW / 2017 / Novel recursive partitioning analysis classification for newly diagnosed glioblastoma : a multi-institutional study highlighting the MGMT promoter methylation and IDH1 gene mutation status / Radiother Oncol 123:106~111
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