Metformin enhances the radiosensitivity of human liver cancer cells to γ–rays and carbon ion beams
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Eun Ho Kim1, Mi-Sook Kim2, Yoshiya Furusawa3, Akiko Uzawa3, Soorim Han1, Won-Gyun Jung1, Sei Sai3
1Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Gongneung-dong, Nowon-Gu, Seoul, South Korea
2Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea
3Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
Mi-Sook Kim, email: [email protected]
Sei Sai, email: [email protected]
Keywords: metformin, carbon ion beam, radiosensitivity, hepatocellular carcinoma cell, DNA damage
Received: August 04, 2016 Accepted: October 19, 2016 Published: October 27, 2016
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.
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