Effect of treatment with melatonin associated with paclitaxel on ovarian carcinoma cells

• Grant number: 20/00544-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2020
• End date: February 28, 2022
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Luiz Gustavo de Almeida Chuffa
• Grantee: Leticia Barbosa Gaiotte
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Ovarian cancer (OC) has a high incidence after menopause and represents a second most common gynecological cancer, second only to cervical cancer. Initially, OC respond to conventional treatments, like paclitaxel (PTX), thus decreasing the tumor mass growth; however, many women develop chemoresistance linked to immune response, and the disease progress with relapse. Melatonin (N-acetyl-5-methoxy-tryptamine) is mostly secreted by the pineal gland, and possesses antioxidant, antitumor and immunomodulatory functions; some of its antitumor properties is linked to their membrane receptors (MT1 and MT2). In menopausal woman, the melatonin secretion decreases with frequent anovulatory cycles thereby increasing the risk of OC development. Therefore, the present study aims to evaluate the effect of functional treatment with melatonin in association with PTX in human ovarian carcinoma cell (SKOV-3). Accordingly, the effects of different doses of melatonin will be investigated (1600 µM, 3200 µM e 4000 µM) associated or not with PTX at different exposure periods using the following parameters: cell counting, cell viability by MTT, cell migration and invasion and apoptosis assay (Annexin-V). Immunofluorescence and western blotting of the PD-L1 immune checkpoint protein as well as the toll-like receptors (TLR2 and TLR4) will also be performed. The immunological factors involved in the immune process: myeloid differentiation factor 88 (MYD88), IFN-³ domain-inducing factor (TRIF), interferon-related nuclear factor (IRF3) and nuclear factor kappaB (NF-kB) will be evaluated by Western blot. In addition, we will investigate the PI3K, AKT, mTOR, ERK1/2 e AP-1 cell survival signaling pathways. These results will contribute to the understanding of how melatonin, acting as a therapeutic adjuvant, may favor PTX chemosensitivity in OC cells. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

GAIOTTE, Leticia Barbosa. Effect of treatment with melatonin associated with paclitaxel in ovarian carcinoma cells. 2022. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.