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

Abstract

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: 5-fluorouracil; MCF-7; chemotherapy; dexamethasone; epirubicin; paclitaxel.

Figure 1

Untreated and dexamethasone (Dex) controls. MCF-7 cells were either untreated (control [CT]) or treated with 100 nM of Dex. The graph indicates the number of cells/mL 3 days after treatment.

Figure 2

Epirubicin with dexamethasone (Dex) pretreatment. MCF-7 cells were pretreated with 100 nM of Dex prior to administration of 25 nM of epirubicin. The graph indicates the number of cells/mL 3 days after treatment. No significant difference was discernible between the samples treated with Dex alone or Dex in combination with epirubicin (n=4). Error bars indicate standard deviation. Abbreviation: NS, nonsignificant.

Figure 3

5-Fluorouracil (5-FU) with dexamethasone (Dex) pretreatment. MCF-7 cells were pretreated with 100 nM of Dex prior to administration of 15 µM of 5-FU. The graph indicates the number of cells/mL 3 days after treatment. No significant difference was discernible between the samples treated with Dex alone or Dex in combination with 5-FU (n=4). Controls not shown (as for Figure 1). Error bars indicate standard deviation. Abbreviation: NS, nonsignificant.

Figure 4

Paclitaxel with dexamethasone (Dex) pretreatment. MCF-7 cells were pretreated with 100 nM of Dex prior to administration of 15 nM of paclitaxel. The graph indicates the number of cells/mL 3 days after treatment. A significant difference was discernible between the samples treated with Dex alone or Dex in combination with paclitaxel (n=4). Error bars indicate standard deviation.