Ovarian cancer has higher incidence in postmenopausal women, and due to its late diagnosis and poor prognosis, is the fourth leading cause of cancer death worldwide, alongside breast, colorectal, lung and cervix cancers. Ovarian cancer initially responds to chemotherapy, slowing the growth of the tumor mass; however, many women can develop chemoresistance to the specific treatment. It is undisputed that risk factors, such as chronic alcoholism, may contribute to tumor aggressiveness, acting as a co-carcinogenic agent. Interestingly, molecular mechanisms related to tumorigenesis and ethanol consumption share the same pathway which potentiates the angiogenesis process and the survival of tumor cells. Given that melatonin possesses oncostatic activities and also seems to inhibit angiogenesis in solid tumors, this study aims to evaluate the effect of ovarian tumor induction and the influence of melatonin therapy on the angiogenesis process via VEGF/VEGFR/HIF in the ovaries of rats that voluntarily consume 10% (v/v) ethanol (UChB strain). For this purpose, the following parameters will be investigated: estrous cycle assessment, frequency and characterization of different types of ovarian tumors through histopathologic analysis, immunoreactivity and quantification of vascular endothelial growth factor receptor 1 (VEGFR1), melatonin receptor 1 (MTR1), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1alpha (HIF-1alpha), and transforming growth factor subtype B1 (TGF-B1), using immunohistochemical techniques and Western blot. These results will assist in clarifying the effects of melatonin on the angiogenesis process and survival of tumor cells associated with ovarian cancer.
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