Kim Eun Ho, Kim Mi-Sook, Furusawa Yoshiya, Uzawa Akiko, Han Soorim, Jung Won-Gyun, Sai Sei
Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Gongneung-dong, Nowon-Gu, Seoul, South Korea.
Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
Oncotarget. 2016 Dec 6;7(49):80568-80578. doi: 10.18632/oncotarget.12966.
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.
本研究的目的是探讨二甲双胍对肝癌（HCC）细胞对γ射线（低线性能量传递（LET）辐射）和碳离子束（高线性能量传递辐射）反应的影响。HCC细胞用二甲双胍预处理，然后接受单剂量的γ射线或碳离子束照射。二甲双胍处理增加了辐射诱导的克隆形成细胞死亡、DNA损伤和细胞凋亡。碳离子束与二甲双胍联合使用在诱导亚G1期和减少G2/M期阻滞、降低波形蛋白表达、增强磷酸化AMPK表达以及抑制磷酸化mTOR和磷酸化Akt方面比单独使用碳离子束或γ射线更有效。因此，二甲双胍有效地增强了不同LET范围辐射的治疗效果，特别是碳离子束，并且可能有助于提高碳离子束的临床疗效。
