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.

Keywords:

• antitumor drugs
• breast cancer stem cells
• CD44
• CD44⁺CD24⁻ cells
• doxorubicin

Acknowledgments

This work was funded by grants from the Vietnam National Project about Breast Cancer, Ministry of Science and Technology, Vietnam. We thank the Oncology Hospital at Ho Chi Minh for supplying the malignant breast cancer tumors.

Disclosure

The authors report no conflicts of interest in this work.