Influence of nanoplastics on the response of ovarian tumor cells to chemotherapy treatment

• Grant number: 24/04120-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Flávia Karina Delella
• Grantee: Geovanna Carla Amaro da Silva
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Polystyrene plastics have become an integral part of human life, and their accumulation representsa significant environmental nuisance. The fragmentation of this material due to exposure toultraviolet radiation, weathering processes, natural mechanical actions, and even biologicaldegradation results in plastic particles of all sizes, ranging from microplastics (MPs, 0.1 ¿m-5mm) to nanoplastics (NPs, <0.1 ¿m). Due to their small size, polystyrene nanoplastics (NPs-PS)are more susceptible to crossing biological membranes and reaching organs, eventuallyaccumulating in tissues and leading to more severe consequences than MPs. Recent literatureconfirms the influence of these materials on oxidative stress in cells, promoting survival andfacilitating tumorigenesis, as well as impacting pathways directly related to chemotherapyresistance in epithelial ovarian cancers (EOC), such as TLRs (toll-like receptors) and JAK/STATpathways induced by IL-6 (interleukin-6). EOC is one of the deadliest neoplasms in thegynecological context, with high-grade serous ovarian cancer (HGSOC) being particularlyaggressive. Despite therapeutic advancements, resistance to conventional chemotherapeutics likecarboplatin (CB) presents a significant challenge in a scenario where disease recurrence is high.The dysregulation of signaling pathways such as JAK/STAT induced by IL-6, TLRs, PI3K-AKT,and MAPK is intrinsically linked to chemotherapy resistance to this drug in EOC cells. In light ofthis, the present project proposes to investigate the influence of NPs-PS on the efficacy of EOCtreatment, exploring possible interactions between NPs-PS and resistance mechanisms to thesedrugs. To this end, cells from the epithelial ovarian cancer line (SKOV-3) will be exposed to NPsPS in three different conditions (isolated, prior to chemotherapy and concomitantly withchemotherapy) to compare parameters such as viability, cytotoxicity, cell migration, invasivepotential, levels of antioxidant enzymes, in addition to analyzing the expression of genes relatedto the resistance of these tumor cells. Human foreskin fibroblasts obtained by primary culture willbe used to analyze the effect of NPs-PS on normal cells. Thus, the results of this study may provideinsights into a possible interaction between NPs-PS and EOC treatment and the influence of thesematerials on resistance mechanisms to these drugs, contributing to the development of moreeffective therapeutic strategies that take into account the effects of these polymers on humantumorigenic cells.