Influence of oncological drugs on PAR1 regulation and its relationship with cardiotoxicity

• Grant number: 25/05896-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Mario Hiroyuki Hirata
• Grantee: Mariane Acauã Santiago Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiotoxicity is a common adverse effect of oncological treatments, which can permanently compromise cardiac function and reduce patient survival. Protease-activated receptor type 1 (PAR1), encoded by the F2r gene, is a G-protein-coupled receptor with essential roles in processes such as hemostasis, inflammation, and vascular responses. It is activated by proteases such as thrombin, cathepsin G, and metalloproteinases. Evidence suggests that PAR1 may be involved in drug-induced cardiac toxicity. This study uses in vitro models to investigate the effects of doxorubicin and sorafenib on F2r expression in HL-1 cells, a murine cardiomyocyte cell line. In parallel, we will analyze cardiotoxic concentrations in 4T1 cells, a mouse breast cancer cell line. Experimental approaches include cell viability assays, RNA extraction, cDNA synthesis, and qPCR, allowing the correlation of gene expression with observed toxicity. In summary, we aim to understand how drugs affect PAR1 and elucidate the mechanisms of cardiotoxicity, this will aid the development of cardioprotective strategies for patients undergoing cancer treatment.