Abstract
Metastasis of cancer cells is initiated by the cellular migration into extracellular matrix and surrounding vessels. We previously showed that elevation of cAMP levels in cancer cells suppressed trans-cellular migration in vitro. Drugs that can elevate cAMP levels in cancer cells effectively may be applied to prevent metastasis in cancer patients. Cilostazol, an oral anti-platelet drug, is a specific cAMP phosphodiesterase type III inhibitor and has been clinically used to treat thrombosis patients. In chemotaxis assay, cellular migration of human colon cancer cells, DLD-1, was induced by 10 μg/ml of soluble fibronectin or 10% of fetal bovine serum (FBS). Treatment with cilostazol (50 μM) suppressed 92.3% or 84.6% of the migration in control cells, respectively. When DLD-1 cells were stimulated by soluble fibronectin in phagokinetic assay, migration assessed by the area of gold particle phagocytosis track was induced and cilostazol also decreased 67.3% of the cellular migration in control cells. Furthermore, in the trans-cellular migration assay, cilostazol suppressed cancer cell invasion induced by FBS. Thus, cilostazol can suppress colon cancer cell motility and might be effective as an anti-metastasis drug for cancer patients.
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Murata, K., Kameyama, M., Fukui, F. et al. Phosphodiesterase type III inhibitor, cilostazol, inhibits colon cancer cell motility. Clin Exp Metastasis 17, 525–530 (1999). https://doi.org/10.1023/A:1006626529536
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DOI: https://doi.org/10.1023/A:1006626529536