In vivo anti-tumor and anti-metastatic activity of renieramycin M and doxorubicin combination treatments on 4T1 breast cancer murine model

Breast cancer continues to be a serious global health concern, necessitating novel treatment approaches. This study explores the potential of combination therapies, investigating the combinatorial effects of doxorubicin (Dox) and renieramycin M (RM) in vivo, previously shown to have synergistic effects in vitro. Single drug administrations and combination treatments were tested on in vivo breast cancer murine models using 4T1-injected BALB/c mice. Tumor volume, animal mortality, and clinical toxicity were monitored, and in silico toxicity assessment was performed. Histopathological analyses using hematoxylin and eosin (H&E) staining, and immunohistochemistry utilizing the p63 breast cancer marker were used for validation. The combination treatment of Dox and RM (5 mg/kg + 1 mg/kg) displayed a 46.53% reduction in tumor volume and an 83.63% decrease in observed metastatic infiltration in the liver. Furthermore, the combination treatment of Dox and RM significantly delayed and reduced the clinical signs of toxicity, as revealed by the decline in observed mortality as opposed to animal deaths in single drug treatments. Our study highlights the potential synergism between Dox and RM as combination therapy for breast cancer treatment. These findings provide possible strategies to improved therapies, offering a more effective and less toxic approach to mitigating breast cancer.