PI3K/AKT/mTOR通路
蛋白激酶B
细胞凋亡
化学
克隆形成试验
DNA损伤
癌症
癌细胞
作者
Tingting Zhang,Long Zhang,Tao Zhang,Jinhai Fan,Kaijie Wu,Zhenfeng Guan,Xinyang Wang,Lei Li,Jer Tsong Hsieh,Dalin He,Peng Guo
出处
期刊:Radiation Research
[BioOne (Radiation Research Society)]
日期:2014-05-20
卷期号:181 (6): 641-649
被引量:30
摘要
Although neo-adjuvant radiotherapy is generally successful in treatment of advanced prostate cancer, radioresistance is still a major therapeutic problem in many patients. In the current study, we investigated the effects of metformin (1,1-dimethylbiguanide hydrochloride), a widely used antidiabetic drug, on tumor cell radiosensitivity in prostate cancer. Through clonogenic survival assays, we found that metformin treatment enhanced radiosensitivity of prostate cancer cells with a dose enhancement factor. Moreover, irradiation of subcutaneous C4-2 tumors in mice treated with metformin resulted in an increase in radiation-induced tumor growth delay (17.3 days to 29.5 days, P < 0.01), which indicates that the tumor radiosensitivity increased by metformin in vivo. We also measured the sublethal damage repair and analyzed double-strand breaks (DSBs) in X-irradiated cells. γ-H2AX, as an indicator of DSBs, had significantly more foci per cell in the group treated with metformin and radiation compared to groups ...
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