Epirubicin-Induced Upregulation of miR-143-3p and miR-145 Enhances Cytotoxicity in MCF-7, MDA-MB-231, and BT-474 Breast Cancer Cell Lines.

Abstract

Drug resistance poses a significant challenge to effective breast cancer chemotherapy. This study investigated the regulatory effects of Epirubicin on miR-143-3p and miR-145 expression in BT-474, MCF-7, and MDA-MB-231 breast cancer cell lines. These miRNAs, known as tumor suppressors, are often downregulated in breast carcinoma, correlating with poorer prognosis. Cells were treated with Epirubicin, and miR-143-3p and miR-145 expression was quantified via qRT-PCR. Epirubicin IC₅₀ values were 0.42 µg/mL (MCF-7), 2.94 µg/mL (MDA-MB-231), and 0.86 µg/mL (BT-474) after 48 h, demonstrating dose- and time-dependent cytotoxicity. Treatment significantly upregulated miR-143-3p and miR-145 expression, with MCF7 cells showing a 3.5-fold increase in miR-145 (p < 0.01) and a 2.8-fold increase in miR-143-3p (p < 0.05) compared to controls. Cell viability decreased by up to 70% at 6 µg/mL Epirubicin in MCF-7 cells, with apoptosis rates rising to 8.65% (MCF-7) and 9.75% (MDA-MB-231) after 24 h (p < 0.01). Colony formation was reduced by 60-80% across cell lines (p < 0.001), and wound closure was inhibited by 40-50% in MDA-MB-231 cells at 24 h (p < 0.0001). These findings suggest that Epirubicin enhances therapeutic efficacy by upregulating miR-143-3p and miR-145, potentially mitigating drug resistance. This highlights their potential as therapeutic targets for improving outcomes in resistant breast cancer subtypes.