THERAPEUTIC POTENTIAL OF ADIPORON AND ITS EFFECTS ON EPITHELIUM-MESENCHYMAL TRANSITION OF PROSTATE CANCER CELL PRIMARY CULTURE

• Grant number: 23/13883-0
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2024
• Effective date (End): February 28, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Sérgio Luis Felisbino
• Grantee: Ana Luiza Romano Gabriel
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Prostate cancer (PCa) remains a significant global health problem, necessitating a deeper understanding of its etiology and potential therapeutic targets. Studies have shown evidence of the association between obesity and a higher incidence of the most aggressive form of PCa at diagnosis. Adipose tissue-derived adipokines, particularly adiponectin, have emerged as key factors in the interaction between obesity and prostate cancer. Adiponectin has well-characterized anti-inflammatory and insulin-sensitizing properties, and has attracted attention for its potential protective role against cancer. Its beneficial effects are mediated through two transmembrane receptors, AdipoR1 and AdipoR2, which can be activated by agonists, such as AdipoRon. Recently, it was observed that AdipoRon is a potent therapeutic strategy for pancreatic, bone and ovarian cancer, however, its action for PCa has not yet been described. Thus, this study seeks to characterize the importance of adiponectin in the progression of PCa by evaluating changes in genes related to the adiponectin hormone pathway and its receptors at different Gleason stages, in addition to elucidating the role of the agonist AdipoRon on the phenomenon of epithelial-mesenchymal transition. . For this, samples from total prostatectomies containing tumors of Gleason grades 3, 4 and 5 and normal areas adjacent to the tumors will be collected from patients operated on at UNIFESP. The tumor fragments will be collected and sliced into parts, which will be immersed in culture medium and digested for subsequent formation of organoids and spheroids. These cells will be treated with 0, 80 and 150 ¼M of AdipoRon for 48 hours for morphological analysis, expression genes and mitochondrial networks. These results will contribute to a better understanding of the involvement of these pathways in prostate cancer, reveal new markers of tumor progression and better risk stratification of patients and potential therapeutic targets for PCa