Dexamethasone reduces side population fraction through downregulation of ABCG2 transporter in MCF-7 breast cancer cells

Abstract

Side population (SP) cells represent a rare population among breast cancer cells. SP cells have been reported to act as cancer stem-like cells and to participate in the development of multidrug resistance via modulating the expression of ATP-binding cassette subfamily G member 2 (ABCG2). Dexamethasone is a corticosteroid drug that has been used as an adjuvant treatment to enhance the efficacy of chemothera-peutic agents; however, its effects in breast cancer have yet to be thoroughly investigated. In the present study, the effects of dexamethasone were investigated using the human MCF-7 breast cancer cell line, and SPs were examined in detail. Cellular proliferation, SP fractions and ABCG2 expression were examined following treatment of MCF-7 cells with dexa-methasone. Dexamethasone was revealed to cause a dose- and time-dependent decrease in cancer cell proliferation, and it also decreased the size of the SP fraction of MCF-7 cells and the expression of the ABCG2 transporter. The effects of dexa-methasone on cellular proliferation, SP fraction and ABCG2 expression were abolished following the administration of the glucocorticoid antagonist RU486. These results suggested that dexamethasone may target breast cancer cell SPs and thus increase the sensitivity of tumor cells to chemotherapy. Therefore, it may be hypothesized that dexamethasone can be used as a chemosensitizer in the adjuvant treatment of patients with breast cancer.