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Article

Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines

  • Authors:
    • Sunbin Ling
    • Tingting Feng
    • Qinghong Ke
    • Ning Fan
    • Lei Li
    • Zhongxing Li
    • Chengyong Dong
    • Cong Wang
    • Fei Xu
    • Yan Li
    • Liming Wang
  • View Affiliations / Copyright

    Affiliations: 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
  • Pages: 2611-2618
    |
    Published online on: April 23, 2014
       https://doi.org/10.3892/or.2014.3151
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Ling S, Feng T, Ke Q, Fan N, Li L, Li Z, Dong C, Wang C, Xu F, Li Y, Li Y, et al: Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines. Oncol Rep 31: 2611-2618, 2014.
APA
Ling, S., Feng, T., Ke, Q., Fan, N., Li, L., Li, Z. ... Wang, L. (2014). Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines. Oncology Reports, 31, 2611-2618. https://doi.org/10.3892/or.2014.3151
MLA
Ling, S., Feng, T., Ke, Q., Fan, N., Li, L., Li, Z., Dong, C., Wang, C., Xu, F., Li, Y., Wang, L."Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines". Oncology Reports 31.6 (2014): 2611-2618.
Chicago
Ling, S., Feng, T., Ke, Q., Fan, N., Li, L., Li, Z., Dong, C., Wang, C., Xu, F., Li, Y., Wang, L."Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines". Oncology Reports 31, no. 6 (2014): 2611-2618. https://doi.org/10.3892/or.2014.3151
Copy and paste a formatted citation
x
Spandidos Publications style
Ling S, Feng T, Ke Q, Fan N, Li L, Li Z, Dong C, Wang C, Xu F, Li Y, Li Y, et al: Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines. Oncol Rep 31: 2611-2618, 2014.
APA
Ling, S., Feng, T., Ke, Q., Fan, N., Li, L., Li, Z. ... Wang, L. (2014). Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines. Oncology Reports, 31, 2611-2618. https://doi.org/10.3892/or.2014.3151
MLA
Ling, S., Feng, T., Ke, Q., Fan, N., Li, L., Li, Z., Dong, C., Wang, C., Xu, F., Li, Y., Wang, L."Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines". Oncology Reports 31.6 (2014): 2611-2618.
Chicago
Ling, S., Feng, T., Ke, Q., Fan, N., Li, L., Li, Z., Dong, C., Wang, C., Xu, F., Li, Y., Wang, L."Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines". Oncology Reports 31, no. 6 (2014): 2611-2618. https://doi.org/10.3892/or.2014.3151
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