TY - JOUR AB - Metformin is an oral anti-hyperglycemic agent of the biguanide family, which is used first-line for type II diabetes with few side-effects. A recent epidemiological study that included 1,828 potential intrahepatic cholangiocarcinoma (ICC) patients showed that metformin use was significantly associated with a 60% reduction in ICC risk in diabetic patients, demonstrating the potential value of metformin in ICC management. In the present study, we firstly showed that metformin exhibited a dose- and time-dependent anti-proliferation effect on ICC cell lines, by mechanisms including apoptosis induction and cell cycle arrest. Metformin targeted the AMPK/mTORC1 pathway in ICC cells. Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As2O3 by targeting the AMPK/mTOR/HIF-1α/MRP1 pathway and ERK. As it is an inexpensive and widely used antidiabetic drug without severe adverse effects, metformin may be a prospective chemotherapeutic agent or a chemosensitizer in future ICC treatment. AD - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, P.R. China Institute of Cancer Stem Cell, Dalian Medical University, Dalian, P.R. China Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, P.R. China College of Basic Medical Sciences, Dalian Medical University, Dalian, P.R. China AU - Ling,Sunbin AU - Feng,Tingting AU - Ke,Qinghong AU - Fan,Ning AU - Li,Lei AU - Li,Zhongxing AU - Dong,Chengyong AU - Wang,Cong AU - Xu,Fei AU - Li,Yan AU - Wang,Liming DA - 2014/06/01 DO - 10.3892/or.2014.3151 EP - 2618 IS - 6 JO - Oncol Rep KW - metformin intrahepatic cholangiocarcinoma cells proliferation chemosensitivity PY - 2014 SN - 1021-335X 1791-2431 SP - 2611 ST - Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines T2 - Oncology Reports TI - Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines UR - https://doi.org/10.3892/or.2014.3151 VL - 31 ER -