Evaluation of the protective effect of melatonin in primary tumor and metastasis in the breast cancer model

Breast cancer is the most common type of cancer in women in the world. It is the metastases performed by tumor cells rather than the primary tumors present in patients. Melatonin is an indole-derived compound, which is secreted by the suprachiasmatic nucleus through the pineal gland, found in many fluids such as blood, saliva and urine. Melatonin has been indicated as a possible oncostatic effects in a different type of cancers, it's anti-proliferative, anti-inflammatory and anti-carcinogenic roles being demonstrated in tumor-related studies. The aim of this study is to evaluate the effect of melatonin administration on primary tumors and metastases by using metastatic breast cancer cells. 4-week-old Balb-C female mice were separated 6 groups. Melatonin treatments were either given before (M1) or after (M2) the injection of 4TLM (4T1 liver metastasis) cells into the mammary pad. Vehicle which was %6 EtOH were also given to control group in compliance with the pre or post melatonin treatment group (M1 and corresponding vehicle group). M1 started a month from the inoculation (M1 and V groups) and continued for approximately 4 weeks after the injection of 4TLM cells. M2 started 1 day after injection of 4TLM cells. Necropsies were performed 27 days after injection of 4TLM. Primary tumors and lung tissues were removed. We performed phenotypes of immune cells in peripheral blood smears obtained tumor-bearing mice. For angiogenesis; primary tumors were evaluated by immunohistochemistry and western blot analysis in terms of angiogenic proteins. Metastasis analysis was performed on liver tissues. In primary tumor and liver tissues, MDSC markers immunoreactivity decreased in melatonin treatment groups compared to TM group. Melatonin treated groups; a significant decrease in the expression of angiogenic markers was demonstrated by both immunohistochemistry and western blot methods. As a result; melatonin treatment decreases tumor development and metastatic response both in primary tumors and tumor microenvironment in the mouse breast cancer model. Anahtar Kelimeler: Breast cancer, melatonin, angiogenesis, immunohistochemistry, western blot