Preexposure of MCF-7 breast cancer cell line to dexamethasone alters the cytotoxic effect of paclitaxel but not 5-fluorouracil or epirubicin chemotherapy

Frederic Buxant,1,* Nadège Kindt,2,* Jean-Christophe Noël,3 Guy Laurent,4,† Sven Saussez2 1Department of Gynaecology, Iris South Hospital, Brussels, 2Department of Anatomy, Laboratory of Anatomy and Cell Biology, Faculty of Medicine and Pharmacy, University of Mons, Mons, 3Department of Pathology, Erasme Hospital, Free University of Brussels (ULB), Brussels, 4Department of Histology, Laboratory of Histology, Faculty of Medicine and Pharmacy, University of Mons, Mons, Belgium *These authors contributed equally to this work †Dr Guy Laurent passed away on August 9, 2016 Purpose: Glucocorticoids (GCs) are often administered prior to any chemotherapeutics to prevent the secondary effects of anticancer agents. Glucocorticoid receptors (GRs) are expressed in several types of cancer cells, particularly in several histological types of breast cancer. Activation of GRs is not associated with any specific cellular response. Both proapoptotic and ­antiapoptotic responses have been observed, depending on the study or the type of breast cancer cells. Therefore, it is of relevance to investigate the possible modulation of apoptotic effect of chemotherapeutic agents when cancerous cells have previously been exposed to GCs. Methods: In vitro cell growth was assayed by counting MCF-7 cells upon exposure to epirubicin (25 nM), 5-fluorouracil (5-FU) (15 µM), and paclitaxel (15 nM), either with or without prior exposure to the GC dexamethasone (Dex) (100 nM).Results: Following preexposure to Dex, the antiapoptotic activity of paclitaxel was significantly reduced by 8.5% (p<0.05), but the activities of epirubicin and 5-FU remained unaltered.Conclusion: In light of the finding that the response of MCF-7 cells pretreated with Dex was significantly reduced, we recommend that the function of GCs should be defined more precisely if they are to be used in conjunction with chemotherapy. Keywords: dexamethasone, 5-fluorouracil, epirubicin, paclitaxel, MCF-7, chemotherapy