The evaluation of Melatonin and EGF interaction on breast cancer metastasis
Abstract Background Breast cancer is currently one of the most common types of cancer in women, and metastasis is the first cause of death in breast cancer patients. The epidermal growth factor (EGF) increases the invasion, growth, and migration of cancer cells. In the present study, melatonin, as a natural hormone, in EGF-induced tumor metastasis, was investigated. Methods First, MDA-MB-231 and MCF7 cells were cultured, and then the effects of melatonin on cell viability were determined by MTT assay. Transwell invasion assay was employed to identify the invasiveness of these breast cancer cell lines. Real-time RT-PCR then investigated the expression of MMP9 and MMP2. Cell proliferation was also determined under EGF and melatonin treatment using Ki67 assessment by flow cytometry. Results The rate of invasion and migration of EGF-treated cells increased in both groups, in which melatonin caused increased invasion by EGF in MCF7 cells. MMP9 and MMP2 expression increased significantly in both cell lines under EGF treatment, and melatonin increased these genes' expression in both cell lines (p <0.05). EGF increased the MMP9 and MMP2 gene expression, and melatonin increases EGF-induced expression(p <0.05). The EGF reduced the expression of the Ki67 protein in the MCF7 cell line, which was negatively affected by Melatonin and EGF. In contrast, along with Melatonin, EGF did not affect the proliferation of the MDA-MB-231 cell line. Conclusions Our results show that melatonin, as a natural compound, can increase the effects of EGF in the proliferation, migration, and invasion of cancer cells at low dosages.