EVALUATION OF THE ANTIANGIOGENIC ACTIVITY OF ZINC IN RENAL ADENOCARCINOMA IN A HYPOXIC MICROENVIRONMENT

• Grant number: 23/06536-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Maria Helena Bellini Marumo
• Grantee: Guilherme Oliveira Carlos
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Renal cell carcinoma (RCC) accounts for approximately 2 to 3% of human malignant tumors and it is the most aggressive urological tumor. The most frequent subtype of RCC is the clear cell (ccRCC) one. Most of the patients with ccRCC have a mutation in the Von Hippel-Lindau (VHL) tumor suppressor gene. The inactivation of the VHL gene interrupts the normal regulation of HIF, leading to altered cellular responses to hypoxia, contributing to increased expression of angiogenic factors and consequent development and progression of CRC. Zinc plays a key role in several biological processes, and has already been shown to be effective in the treatment of several types of cancer. The present project consists in analyzing the antiangiogenic activity of zinc chloride (ZnCl2) in renal cell carcinoma in a hypoxic microenvironment aiming at clarifying the pathophysiological mechanisms of this element in renal carcinogenesis. For this, the project will include the evaluation of gene expression: HIF1±, HIF2±, VEGFR-1, VEGFR-2, VEGF-±, TGF-², IL-6, IL-8 and CARBONIC ANHYDRASE in cell line 786-0 in normoxia and hypoxia using RT-qPCR and western blotting techniques.