title: Metformin Inhibits Migration and Invasion of Cholangiocarcinoma Cells
abstract: Background: Metformin is an oral anti-diabetic agent that has been widely prescribed for treatment of type II diabetes.
  Anti-cancer properties of metformin have been revealed for numerous human malignancies including cholangiocarcinoma
  (CCA) with anti-proliferative effects in vitro. However, effects on CCA cell migration and invasion have not been
  fully investigated. The present study aimed to explore the inhibitory effects of metformin on motility, migration and
  invasion of the CCA cell line HuCCT1, and examine molecular mechanisms underlying metformin effects. Methods:
  HuCCT1 cells were exposed to increasing doses of metformin. Viability and growth of HuCCT1 cells were assessed
  by MTS and colony formation assays, respectively. Motility, migration and invasion of metformin-treated HuCCT1
  cells were determined in vitro using wound healing, transwell migration and matrigel invasion assays. Expression of
  signaling molecules and epithelial-mesenchymal transition (EMT) markers was assessed by Western blotting. Results:
  It was observed that metformin significantly decreased HuCCT1 cell viability and colony formation. The agent also
  markedly reduced wound closure, migration and invasion of HuCCT1 cells. Furthermore, metformin exposure resulted
  in decreased STAT3 activation and down-regulation of anti-apoptotic protein Bcl-2 and Mcl-1 expression. In addition,
  it upregulated the expression of E-cadherin, while downregulating that of N-cadherin, Snail, and MMP-2. Conclusion:
  These results demonstrated inhibitory effects of metformin on CCA cell migration and invasion, possibly involving
  the STAT3 pathway and reversal of EMT markers expression. They further suggest that metformin may be useful for
  CCA management.
authors.affiliation: Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand. Email:waraporn.cho@mahidol.ac.th
authors.forename: Son Xuan
authors.initials: SX
authors.lastname: Trinh
authors.forename: Huyen Thi Bich
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Kween
authors.initials: K
authors.lastname: Saimuang
authors.forename: Virapong
authors.initials: V
authors.lastname: Prachayasittikul
authors.forename: Waraporn
authors.initials: W
authors.lastname: Chan On
keywords: Cholangiocarcinoma; metformin; migration; invasion; STAT3; EMT