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Chloroquine exerts anti-metastatic activities under hypoxic conditions in cholangiocarcinoma cells.
- Source :
-
Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2015; Vol. 16 (5), pp. 2031-5. - Publication Year :
- 2015
-
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 (CoCl2)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to 100 μM CoCl2. 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-1α) 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-1α/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.
- Subjects :
- Cadherins metabolism
Cell Line, Tumor
Cell Movement drug effects
Cholangiocarcinoma metabolism
Cholangiocarcinoma pathology
Epithelial-Mesenchymal Transition drug effects
Humans
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Neoplasm Metastasis pathology
Neovascularization, Pathologic drug therapy
Neovascularization, Pathologic metabolism
Neovascularization, Pathologic pathology
Vascular Endothelial Growth Factor A metabolism
Angiogenesis Inhibitors pharmacology
Cell Hypoxia drug effects
Chloroquine pharmacology
Cholangiocarcinoma drug therapy
Neoplasm Metastasis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2476-762X
- Volume :
- 16
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Asian Pacific journal of cancer prevention : APJCP
- Publication Type :
- Academic Journal
- Accession number :
- 25773848
- Full Text :
- https://doi.org/10.7314/apjcp.2015.16.5.2031