The Co-Administration of Fluoroquinolones Strongly Increases the Anticancer Efficacy of Carboplatin Treatment-Novel Insights for Breast Cancer Chemotherapy from the Canine Mammary Tumor Model

: Human breast cancer (HBC) is the most common and often lethal malignancy in women. Canine mammary tumors (CMTs) share significant molecular and clinical characteristics with HBC, which makes dogs a valuable spontaneous model for the study of HBC. HBC chemotherapy treatment relies mainly on carboplatin, which is effective but, in turn, highly toxic. Here we tested enrofloxacin, a Minichromosomal Maintenance Complex Component (MCM2) inhibitor, for its ability to increase tumor cell sensitivity to platinum-based drugs, thus suggesting a potential synergistic therapeutic strategy. CMT samples were used to establish primary cell cultures. Cells were treated with carboplatin, enrofloxacin, and their combination at different concentrations. Cytotoxic and antiproliferative effects were assessed using xCELLigence and MTT assays. Single-drug treatments exert limited effects on cell proliferation, while enrofloxacin significantly enhances carboplatin efficacy, leading to a complete growth arrest within 48 h. The MTT assay confirms a strong synergistic effect of the two drugs, whereas the Dose Reduction Index analysis indicates that carboplatin could be decreased without losing effectiveness. These findings suggest that combined therapy could represent a more effective and less toxic option for HBC and CMTs. This work also strengthens the possible use of the canine model for cancer studies within a One Health framework.