Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Trichostatin A, a Histone Deacetylase Inhibitor, Potentiated Cytotoxic Effect of ionizing Radiation in Human Head and Neck Cancer Cell Lines

히스톤탈아세틸효소 억제제 Trichostatin A에 의한 인간 두경부암 셰포주의 방사선 감수성 증강

  • Kim, Jin Ho (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Shin, Jin Hee (Department of Cancer Research Institute, Seoul National University College of Medicine) ;
  • Chie, Eui Kyu (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Wu, Hong-Gyun (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Kim, Jae Sung (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Kim, Il Han (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Ha, Sung Whan (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Park, Charn Il (Department of Radiation Oncology, Seoul National University College of Medicine) ;
  • Kang, Wee-Saing (Department of Radiation Oncology, Seoul National University College of Medicine)
  • 김진호 (서울대학교 의과대학 방사선종양학교실) ;
  • 신진희 (서울대학교 의과대학 암연구소) ;
  • 지의규 (서울대학교 의과대학 방사선종양학교실) ;
  • 우홍균 (서울대학교 의과대학 방사선종양학교실) ;
  • 김재성 (서울대학교 의과대학 방사선종양학교실) ;
  • 김일한 (서울대학교 의과대학 방사선종양학교실) ;
  • 하성환 (서울대학교 의과대학 방사선종양학교실) ;
  • 박찬일 (서울대학교 의과대학 방사선종양학교실) ;
  • 강위생 (서울대학교 의과대학 방사선종양학교실)
  • Published : 2004.06.01
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Abstract

Purpose : We have previously reported that human glioblastoma cells are sensitized to radiation-induced death after their exposure to trichostatin A (TSA), a histone deacetylase inhibitor (HDAC-1), prior to the irradiation. We aimed to measure the magnitude of the radiosensitizing effect of TSA in human head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines, HN-3 and HN-9, were exposed to 0, 50, 100, and 200 nM TSA for 18 hr prior to irradiation. Then, the TSA-treated cells were irradiated with 0, 2, 4, 6, and 8 Gy, and cell survival was measured by clonogenic assay. Results : Pre-irradiation exposure to TSA was found to radiosensitize HN-3 and HN-9 cell lines. In HN-9 cells, the fraction surviving after 2 Gy (SF2) was significantly reduced by treatment of TSA at concentration as low as 50 nM. However, a treatment with 200 nM TSA was required to significantly decrease SF2 in the HN-3 cell line. SER of pre-irradiation treatment with 200 nM TSA was 1.84 in HN-3 and 7.24 in HN-9, respectively. Conclusions : Our results clearly showed that human head and neck cancer cell lines can be sensitized to ionizing radiation by pre-irradiation inhibition of histone deacetylase (HDAC) using TSA, and that this potentiation might well be a general phenomenon.

목적 : 본 연구진이 기왕에 입증한 바 있는 히스톤탈아세틸효소 억제제 trichostatin A (TSA)가 나타내는 방사선 감수성 증강 작용이 두경부암 세포주에서 발생하는 정도를 실험적으로 확인하고자 하였다. 대상 및 방법 : 인간 두경부암 세포주인 HN-3과 HN-9를 0, 50, 100, 200 nM의 TSA에 18시간 동안 전처치시킨 후 각각 0, 2, 4, 6, 8 Gy 방사선을 조사하였다. 세포생존곡선은 clonogenic assay를 이용하여 산출하였고 linear quadratic 모델에 따라 분석하였다 결과 : 방사선 조사 전 TSA처리는 HN-3과 HN-9 세포주의 방사선 감수성을 증강시켰다. 50 nM의 TSA로 처리된 HN-9 세포주에서 2 Gy 조사후 생존분획(SF2)은 유의한 수준으로 감소하였으나, HN-3 세포주는 200 nM의 TSA 처리 후 SF2가 유의하게 감소하였다. HN-3과 HN-9 세포주에서 200 nM TSA의 sensitizer enhancement ratio는 각각 1.84와 7.24였다. 결론 : 방사선 조사 전 히스톤탈아세틸효소 억제는 인간 두경부암 세포주의 방사선 감수성을 증가시켰으며, 이 증강 작용이 암세포주에서의 일반적으로 관찰되는 현상일 가능성이 크다고 제안한다.

Keywords

References

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