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The aim of this study was to compare the differential effects of standard chemotherapy regimens (FEC: 5\u2010fluorouracil plus epirubicine plus cyclophosphamide) in combination with epigenetic modulators (decitabine, valproic acid): (a) on gene methylation levels of selected tumour biomarkers (LINE\u20101, uPA, PAI\u20101, DAPK); (b) their expression status (uPA and PAI\u20101); (c) differentiation status (5meC and H3K27me3). Furthermore, cell survival as well as changes concerning the invasion capacity were monitored in cell culture models of breast cancer (MCF\u20107, MDA\u2010MB\u2010231). A significant overall decrease of cell survival was observed in the FEC\u2010containing combination therapies for both cell lines. Methylation results showed a general tendency towards increased demethylation of the uPA and PAI\u20101 gene promoters for the MCF\u20107 cells, as well as the proapoptotic DAPK gene in the treatment regimens for both cell lines. The uPA and PAI\u20101 antigen levels were mainly increased in the supernatant of FEC\u2010only treated MDA\u2010MB\u2010231 cells. DAC\u2010only treatment induced an increase of secreted uPA protein in MCF\u20107 cell culture, while most of the VPA\u2010containing regimens also induced uPA and PAI\u20101 expression in MCF\u20107 cell fractions. Epigenetically active substances can also induce a re\u2010differentiation in tumour cells, as shown by 5meC, H3K27me3 applying ICC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance of the study<\/jats:title><jats:p>Epigenetic modulators especially in the highly undifferentiated and highly malignant MDA\u2010MB\u2010231 tumour cells significantly reduced tumour malignancy thus; further clinical studies applying specific combination therapies with epigenetic modulators may be warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbf.3626","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T22:29:51Z","timestamp":1613860191000},"page":"571-583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epigenetic modulators combination with chemotherapy in breast cancer 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