The Therapeutic Effect of Raloxifene and Fluoxetine in the Rat Model of Breast Cancer

The worldwide rate of breast cancer is constantly increasing, so it is important to develop therapeutic drugs that can be used in the treatment of breast cancer. In our study, the potential therapeutic effects of Raloxifene and Fluoxetine on breast cancer induced by DMBA alone or in combination were investigated. 32 Wistar Albino female rat divided into four groups; DMBA (Group I), DMBA+RAL (Group II), DMBA+FLX (Group III), DMBA+RAL+FLX (Group IV). The levels of VEGF, M-CSF, MMP-9 and TIMP-1 in breast tissue and plasma were determined by ELISA method. MDA and GSH levels with SOD, GSH-Px and CAT activities in breast cancer tissues were determined using spectrophotometer. When the plasma CA 15-3 levels of the study groups were compared with the DMBA group, it was seen to decrease significantly in all treatment groups. Plasma VEGF levels were significantly reduced in all treatment groups, while reductions in plasma M-CSF levels in these groups were not significant. A significant decrease in plasma MMP-9 levels was observed only in the RAL + FLX group. Plasma TIMP-1 levels were significantly reduced in all treatment groups compared to the DMBA group. A reduction in tissue CA 15-3, VEGF, M-CSF and MMP-9 levels of the all treatment groups was observed compared to the DMBA group. While the decrease in CA 15-3 and M-CSF levels in all treatment groups was statistically significant, VEGF levels are statistically significant only in the RAL + FLX group. In addition, the most significant decrease in MMP-9 levels was observed in the RAL-treated group, while a significant increase in TIMP-1 levels was observed only in the RAL+FLX group. Compared to the DMBA group; tissue MDA levels were significantly decreased in all treatment groups except the FLX group, whereas tissue SOD, GSH-Px and CAT activities were increased in all treatment groups. Only the increase in GSH-Px and CAT activities in the RAL + FLX group was statistically significant. Tissue GSH levels were significantly increased in the RAL and RAL + FLX groups. In conclusion, it is thought that the combined use of RAL and FLX in DMBA-induced breast cancer tissues can modulate the progression of breast cancer so that it can suppress angiogenesis and oxidative stress more effectively, reduce the presence of activated macrophages in tumors.