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Chloroquine Exerts Anti-metastatic Activities Under Hypoxic Conditions in Cholangiocarcinoma Cells

  • Thongchot, Suyanee (Department of Biochemistry, Khon Kaen University) ;
  • Loilome, Watcharin (Department of Biochemistry, Khon Kaen University) ;
  • Yongvanit, Puangrat (Department of Biochemistry, Khon Kaen University) ;
  • Dokduang, Hasaya (Department of Biochemistry, Khon Kaen University) ;
  • Thanan, Raynoo (Department of Biochemistry, Khon Kaen University) ;
  • Techasen, Anchalee (Department of Biochemistry, Faculty of Associated Medical Sciences, Khon Kaen University) ;
  • Namwat, Nisana (Department of Biochemistry, Khon Kaen University)
  • Published : 2015.03.18

Abstract

Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial-mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride ($CoCl_2$)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to $100{\mu}M$ $CoCl_2$. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-$1{\alpha}$/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.

Keywords

Hypoxia;chloroquine;EMT;metastasis;cholangiocarcinoma

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