Ovarian tumor induction and the influence of melatonin on Her 2 and 4 receptors signaling pathways in UChB rats

Abstract

Ovarian cancer has the highest incidence in peri-and postmenopausal, and due to its late diagnosis and poor prognosis, it is the fourth leading cause of cancer death worldwide, alongside breast, colorectal, lung and cervix cancers. Ovarian cancer initially responds to conventional chemotherapy, slowing the growth of the tumor mass, however, in an unexpected way, many women can develop chemoresistance to 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 promotes the survival and proliferation of tumor cells. Given that melatonin possesses immunomodulatory and oncostatic activities and also seems to inhibit cell proliferation-related Her signaling pathway, this study aims to evaluate the effect of ovarian tumor induction and the influence of melatonin on Her 2 and 4-mediated signaling 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 monitoring, evaluation of the frequency and characterization of different types of ovarian tumors through histopathology, immunoreactivity and quantification of Her 2 and 4-target receptors, and proteins/enzymes like phosphatidylinositol 3 kinase (PI3K), AKT protein (protein kinase B), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) using immunohistochemical techniques and Western blot. These results will assist in clarifying the effects of melatonin on the proliferation and survival of tumor cells associated with ovarian cancer. (AU)