The effect of doxorubicin (DOX) and Memantine on breast cancer in mice modeled with 4T1 cells

Abstract

Breast cancer is one of the most common cancers diagnosed among all malignancies in the world. This tumor is the second most common type of cancer among women, which has a large annual mortality rate. Doxorubicin is a chemotherapy drug that is widely used in the treatment of breast cancer patients. Doxorubicin’s side effects, including cardiotoxicity, cause its consumption to face limitations. In recent years, memantine has shown cardioprotective and anticancer effects. In this study, we decided to investigate the effect of simultaneous drug therapy with doxorubicin and memantine on mice modeled with breast cancer. Materials and methods: 4T1 cell line was used for tumor inoculation. After the tumor’s volume reached a certain level, they were randomly divided into 4 groups of 3 each. One group received physiological serum as a control group throughout the study. One group received only 5mg/kg doxorubicin in 4 doses, the next group received 20mg/kg memantine in 15 doses, and the last group received both doxorubicin and memantine with the mentioned doses. Finally, after one month, the mice were sacrificed and the lung tissue, liver tissue was isolated to check for metastasis and their heart to check for MPO, MDA and TNF-α factors. Tumors were also isolated from surrounding tissues and kept for TUNEL test. Results: The results of this study showed that adding memantine to the treatment regimen of mice receiving doxorubicin significantly reduced MDA and TNF-α levels. On the other hand, the tunnel test results showed that the highest rate of tumor cell apoptosis was in the group receiving memantine and doxorubicin at the same time. Memantine has significantly reduced tumor volume and weight compared to the control group. Pathology results also showed that simultaneous treatment with doxorubicin and memantine reduced the number and size of metastatic nodules. Also, no atrophy changes were observed in the cardiac histopathological section which received memantine.