Downregulation of CD44 reduces doxorubicin resistance of CD44+CD24- breast cancer cells

Abstract

BACKGROUND: Cells within breast cancer stem cell populations have been confirmed to have a CD44(+)CD24(-) phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells. METHODS: In this study, we reduced CD44 expression in CD44(+)CD24(-) breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44(+)CD24(-) breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug. RESULTS: The proliferation of CD44 downregulated CD44(+)CD24(-) breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups. CONCLUSIONS: It would appear that expression of CD44 is integral among the CD44(+)CD24(-) cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy.