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http://dx.doi.org/10.7314/APJCP.2015.16.5.2031

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.5, 2015 , pp. 2031-2035 More about this Journal
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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