title: Metformin enhances the radiosensitivity of human liver cancer cells to γ-rays and carbon ion beams.
abstract: The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ-rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ-rays or carbon ion beams. Metformin treatment increased radiation-induced clonogenic cell death, DNA damage, and apoptosis. Carbon ion beams combined with metformin were more effective than carbon ion beams or γ-rays alone at inducing subG1 and decreasing G2/M arrest, reducing the expression of vimentin, enhancing phospho-AMPK expression, and suppressing phospho-mTOR and phospho-Akt. Thus, metformin effectively enhanced the therapeutic effect of radiation with a wide range of LET, in particular carbon ion beams and it may be useful for increasing the clinical efficacy of carbon ion beams.
authors: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Gongneung-dong, Nowon-Gu, Seoul, South Korea.
authors: Eun Ho
authors: EH
authors: Kim
authors: Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
authors: Mi-Sook
authors: MS
authors: Kim
authors: Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
authors: Yoshiya
authors: Y
authors: Furusawa
authors: Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
authors: Akiko
authors: A
authors: Uzawa
authors: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Gongneung-dong, Nowon-Gu, Seoul, South Korea.
authors: Soorim
authors: S
authors: Han
authors: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Gongneung-dong, Nowon-Gu, Seoul, South Korea.
authors: Won-Gyun
authors: WG
authors: Jung
authors: Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
authors: Sei
authors: S
authors: Sai
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D063193:Heavy Ion Radiotherapy; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008687:Metformin / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
chemical_list: D011838:Radiation-Sensitizing Agents; D014746:Vimentin; D008687:Metformin; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: DNA damage; carbon ion beam; hepatocellular carcinoma cell; metformin; radiosensitivity