@article{oai:repo.qst.go.jp:00047641,
 author = {EunHo, Kim and Mi-Sook, Kim and 古澤, 佳也 and 鵜澤, 玲子 and Soorim, Han and Won-Gyun, Jung and 崔, 星 and Ｋｉｍ Ｅｕｎ Ｈｏ and 古澤 佳也 and 鵜澤 玲子 and 崔 星},
 issue = {7},
 journal = {Oncotarget},
 month = {Oct},
 note = {ABSTRACT
Purpose: 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).
Methods: Huh-7 and HepG2 cells were pretreated with metformin and exposed to a single dose of fraction γ–rays or carbon ion beams (13 and 70keV/μm). Cell survival, DNA repair, apoptosis, cell cycle progression, migration, invasion and the AMPK/mTOR/Akt signaling pathway were assessed.
Results: Irradiation with γ-rays and carbon ion beams decreased the clonogenic survival of HCC cells in a dose-dependent manner, and metformin significantly increased radiation-induced clonogenic cell death. The relative biological effectiveness (RBE) of Huh7 (HepG2) cells at 13 and 70keV/μm carbon ion beams relative to γ-rays at the D10 levels was approximately 1.68 (1.11) and 2.37 (2.00), respectively.
The γH2AX and comet assays showed that 70keV/μm carbon ion beams induced DNA damage more effectively than 13keV/μm carbon ion beams. Metformin significantly enhanced the DNA damage caused by irradiation, particularly that of 70keV/μm carbon ion beams. Higher levels of apoptosis were induced by 70keV/μm carbon ion beams than by 13keV/μm carbon ion beams and γ-rays, and metformin increased radiation-induced apoptosis. Carbon ion beams combined with metformin more effectively induced subG1 and G2/M arrest, reduced the expression of N-cadherin and vimentin, enhanced phospho-AMPK expression and downregulated phospho-mTOR and phospho-Akt than carbon ion beams or γ-rays alone.},
 pages = {80568--80578},
 title = {Metformin enhances the radiosensitivity of human liver cancer cells to γ–rays and carbon ion beams},
 volume = {49},
 year = {2016}
}