TY - JOUR ID - 30703 TI - Chloroquine Exerts Anti-metastatic Activities Under Hypoxic Conditions in Cholangiocarcinoma Cells JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 Y1 - 2015 PY - 2015 VL - 16 IS - 5 SP - 2031 EP - 2035 KW - hypoxia KW - chloroquine KW - EMT KW - Metastasis KW - cholangiocarcinoma DO - N2 - Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelialmesenchymaltransition that accounts for a major mechanism of metastasis. Chloroquine potentially offers anew therapeutic approach with an ‘old’ drug for effective and safe cancer therapies, as it exerts anti-metastaticactivity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration undercobalt chloride (CoCl2)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration underhypoxic-mimicking conditions on exposure to 100 μM CoCl2. Moreover, chloroquine stabilized the protein levelof prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such ashypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF). It also suppressed epithelialmesenchymal 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-1α/VEGF/EMT which may serveas a useful additional strategy for CCA therapy. UR - https://journal.waocp.org/article_30703.html L1 - https://journal.waocp.org/article_30703_0903c4afd2ffe8e32ce87294978b408d.pdf ER -