Epigenetic drugs are promising add-ons to
cancer treatment; still, adverse effects concerning tumour promotion have been reported occasionally. In this in vitro study, we investigated the effect of combination treatment of
decitabine with
anthracycline-based
chemotherapy [
5-fluorouracil plus epirubicine plus
cyclophosphamide (FEC)] on viability and metastatic activity of
breast cancer cell lines, MDA-MB-231 (
estrogen receptor-negative) and MCF-7 (
estrogen receptor-positive). The effect of
decitabine and its combined treatment with FEC on viability of both
cancer cell lines was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide and
adenosine triphosphate (
ATP) cell survival assays. DNA methylation specific real-time polymerase chain reaction (PCR) (Methylight®) was employed to document the methylation status of the
metastasis-relevant
urokinase-type plasminogen activator (uPA) and
plasminogen activator inhibitor-I (PAI-1) genes. Additionally,
protein expression levels of uPA and
PAI-1 were determined using
enzyme-linked
immunosorbent assays. Invasion capacity of cells was assayed using Matrigel® invasion assay.
Decitabine lowered the viability of MCF-7 cells, although MDA-MB-231 cells were not affected.
Decitabine did not augment FEC-mediated cytotoxicity in both cell lines. In MCF-7 cells, methylation of the uPA and
PAI-1 gene promoter was significantly reduced by
decitabine or
decitabine plus FEC.
Protein levels of uPA and
PAI-1 were induced by all treatments.
Decitabine significantly induced the invasion capacity of MCF-7 cells, whereas all of the drugs resulted in decreased invasion capacity of MDA-MB-231. Our results suggest differential effects of single-dose
decitabine and its combination with FEC on the metastatic capacity and survival of
breast cancer cell lines endowed with different metastatic behaviour.