The role of adiponectin on prostate cancer development associated with obesity in Adipoq-/- mice and potential therapeutic action of adiporon

• Grant number: 21/07979-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2021
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Morphology - Histology
• 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

Obesity increases the propensity to develop other diseases, such as hypertension and dyslipidemia, in addition to several types of cancer, including prostate cancer (CaP). Excess of adipose tissue is responsible for altering the production and secretion of various adipokines, such as adiponectin. This adipokine has anti-diabetic, anti-inflammatory, and cardioprotective effects, however, currently, studies show that low serum levels of adiponectin are associated with a higher incidence of the more aggressive form of PCA. 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 CaP has not yet been described. Thus, this study seeks to characterize the importance of adiponectin in the risk of developing prostate cancer in association with obesity, in addition to revealing whether the agonist AdipoRon can be used in the personalized treatment of PC, especially for the metastatic and androgen-independent form. For this, C57BL/6 male mice (WT) and adiponectin knockouts (AdKO) fed with a control and high-fat diet will be used. After 6 months of diet, the ventral prostate will be collected for morphological, immunohistochemical, histopathological, and molecular analyses. In vitro, two human prostate cell lines will be also used, one normal (PNT-2) and one tumor independent of androgen (PC3). These cells will be treated with 0, 75, and 150 µM of AdipoRon for 24 and 48 hours for analysis of cell migration and invasion.(AU)