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  • [Radiat Res.] The Efficacy of Radiation is Enhanced by Metformin and Hyperthermia Alone or Combined Against FSaII Fibrosarcoma in C3H Mice

    KIRAMS / 김현경, 김미숙*

  • 출처
    Radiat Res.
  • 등재일
    2022 Aug 1
  • 저널이슈번호
    198(2):190-199. doi: 10.1667/RADE-21-00231.1.
  • 내용

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    Abstract
    The effects of mild-temperature hyperthermia (MTH) and metformin, alone or in combination, on the efficacy of high-dose hypofractionated radiation against experimental tumors were investigated. FSaII fibrosarcoma grown subcutaneously in the hind legs of C3H mice was irradiated with a single 15 Gy dose using a 60Co irradiator. The radio frequency capacitive method was used to heat the tumors at 41.0°C for 30 min. Metformin was intraperitoneally (i.p.) administered daily to tumor-bearing mice at a dose of 150 mg/kg. The expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and programmed cell death-ligand 1 (PD-L1) were determined by immunohistochemical staining of the excised tumor tissues. The apoptosis of tumor cells in vivo was quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and cleaved caspase-3 staining of the excised tumor tissues. Irradiation of tumors markedly increased the expression of HIF-1α, VEGF, and PD-L1, and MTH and metformin used either alone or in combination significantly abrogated the radiation-induced upregulation of these proteins. MTH and metformin alone or combined increased the radiation-induced apoptosis in tumor cells and enhanced the radiation-induced suppression of tumor growth. The findings indicated that the increased tumor response to 15 Gy irradiation by MTH and metformin alone or in combination was due, in part, to the abrogation of the radiation-induced upregulation of HIF-1α and its downstream targets VEGF and PD-L1.

     

     

    Affiliations

    Hyunkyung Kim  1   2 , Dohyeon Kim  1   2 , Wonwoo Kim  1 , EunJi Kim  3 , Won Il Jang  3 , Mi-Sook Kim  3   2
    1 Clinical Translational Research Team, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.
    2 Department of Radiological & Medico-Oncological Science, University of Science and Technology, Daejeon, Korea.
    3 Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.

  • 편집위원

    본 연구는 섬유육종 마우스모델에서 당뇨약인 Metformin과 온열치료가 방사선치료의 효율에 미치는 영향에 관해 평가한 연구이다. Metformin과 온열치료는 단독처리와 병용처리 모두에서 방사선치료 효율을 증대시켰으며, 그 메커니즘을 밝혔다.

    2022-10-06 10:09:30

  • 편집위원2

    metformin과 Hyperthermia의 병용처리시, 방사선에 의한 영향에 대한 논문임. Hyperthermia와 metformin 병용처리에 대한 연구가 많이 알려져 있지 않으며, 또한, 이에 대한 방사선 효과에 대한 연구 결과도 흥미롭다고 생각함

    2022-10-06 10:09:51

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