Reducing Doxorubicin resistance in breast cancer by liposomal FOXM1 aptamer: In vitro and in vivo

Abstract

Aims: Drug resistance is one of the main obstacles in cancer chemotherapy. The forkhead box M1 (FOXM1) is a transcription factor and its overexpression in breast cancer is related to resistance to chemotherapy. In this study, we prepare liposomal FOXM1 aptamer (Lip-FOXM1apt) and evaluate its effects on Doxorubicin (Dox) resistance in vitro and in vivo.

Main methods: MTT assay, cell association, cellular uptake, Annexin V-FITC/PI dual staining assay were investigated in MDA-MB-231, MCF-7, 4T1. In vivo studies were performed in 4T1 tumor-bearing BALB/c mice.

Key findings: We found that the combination therapy of Dox and Lip-FOXM1apt significantly increases both Dox cytotoxicity on cancer cells as well as Dox-induced apoptosis. Administering Lip-FOXM1apt remarkably improved the anti-tumor efficacy of Dox in mice model that was strikingly more effective than Dox monotherapy.

Significance: Taken together, this study provides a new strategy to overcome Dox resistance and merits further investigation.

Keywords: Breast cancer; Doxorubicin; Doxorubicin resistance; FOXM1 aptamer; Liposomal formulation.