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Benefits of Metformin Use for Cholangiocarcinoma

  • Kaewpitoon, Soraya J (School of Family Medicine and Community Medicine, Suranaree University of Technology) ;
  • Loyd, Ryan A (School of Family Medicine and Community Medicine, Suranaree University of Technology) ;
  • Rujirakul, Ratana (Suranaree University of Technology Hospital) ;
  • Panpimanmas, Sukij (Suranaree University of Technology Hospital) ;
  • Matrakool, Likit (Suranaree University of Technology Hospital) ;
  • Tongtawee, Taweesak (Suranaree University of Technology Hospital) ;
  • Kootanavanichpong, Nusorn (Faculty of Public Health, Vongchavalitkul University) ;
  • Kompor, Ponthip (Faculty of Public Health, Vongchavalitkul University) ;
  • Chavengkun, Wasugree (Faculty of Public Health, Vongchavalitkul University) ;
  • Kujapun, Jirawoot (Faculty of Public Health, Vongchavalitkul University) ;
  • Norkaew, Jun (Faculty of Public Health, Vongchavalitkul University) ;
  • Ponphimai, Sukanya (Faculty of Public Health, Vongchavalitkul University) ;
  • Padchasuwan, Natnapa (Faculty of Public Health, Khon Kaen University) ;
  • Pholsripradit, Poowadol (Provincial Public Health Office of Nakhon Ratchasima) ;
  • Eksanti, Thawatchai (Nakhon Ratchasima Rajabhat University) ;
  • Phatisena, Tanida (Nakhon Ratchasima Rajabhat University) ;
  • Kaewpitoon, Natthawut (Parasitic Disease Research Unit, Suranaree University of Technology)
  • Published : 2016.01.11

Abstract

Metformin is an oral anti-hyperglycemic agent, which is the most commonly prescribed medication in the treatment of type-2 diabetes mellitus. It is purportedly associated with a reduced risk for various cancers, mainly exerting anti-proliferation effects on various human cancer cell types, such as pancreas, prostate, breast, stomach and liver. This mini-review highlights the risk and benefit of metformin used for cholangiocarcinoma (CCA) prevention and therapy. The results indicated metformin might be a quite promising strategy CCA prevention and treatment, one mechanism being inhibition of CCA tumor growth by cell cycle arrest in both in vitro and in vivo. The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin. Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. Clinical trials and epidemiological studies of the benefit of metformin use for CCA should be conducted. To date, whether metformin as a prospective chemotherapeutic for CCA is still questionable and waits further atttention.

Keywords

Metformin;cholangiocarcinoma;bile duct cancer;gall bladder cancer

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