The goal of this study was to mechanistically analyze the effects of pre-treatment or post-treatment melatonin on the metastatic spread in a mice model. Consequently, the effects on the tumor growth, angiogenesis and metastasis were evaluated with immunohistochemical and western blot analysis. 8-10 weeks-old female BALB/c mice (n = 60, 10/group) were used. Liver metastatic cells (4TLM) from 4T1 murine breast carcinoma were previously isolated. Melatonin was administrated either before or after the injection of 4TLM cells into the mammary pad. Tumor and vehicle (%6 ethanol) injections were given to vehicle groups. Tumor group consisted of the mice injected with only 4TLM cells injected to tumor group and no intervention to control group. Necropsies were performed 27 days after injection of 4TLM. Primary tumors and metastatic tissues were removed. Furthermore, changes in lung and liver metastasis and primary tumor growth and angiogenesis were evaluated. In our study neutrophil levels were noted to be increased in peripheral blood of the tumor-bearing mice. Melatonin exerted inhibitory effects on the 4TLM-induced leukocytosis. Melatonin significantly decreased lung and liver metastasis, primary tumor growth and angiogenesis. The results demonstrated that melatonin might have a therapeutic role through reducing systemic inflammatory responses, metastasis, tumor growth and angiogenesis.
Keywords: Pre and post administration of melatonin; breast cancer; metastasis; mice.