Prostate cancer and oxidative stress: analysis of expression and therapeutic potential of the enzyme sulfiredoxin

Abstract

Prostate cancer (PCa) is the second most frequent and the second highest rate of morbidity and mortality among men. Studies highlight the role of oxidative stress in the initiation and progression of PCa. Analysis of transcriptomes from knockout mice for prostate cancer showed changes in oxidative stress genes, such as increased expression of the sulfiredoxin (Srxn1) gene, for which there is no report in PCa yet. Thus, the aim of this project is to characterize the Srxn expression in the human PCa, as well to investigate if this enzyme is a potential therapeutic target. For this, it will be evaluated by immunohistochemistry the protein expression levels of Srxn in TMAs blocks containing samples of CaP at different Gleason grade and to correlate the results with patient clinical data. It will be analyzed the levels of gene and protein expression of Srxn1 by normal (RWPE-1) and tumoral prostate cell lines (LNCaP and PC3) at different culture conditions, besides the cellular viability of LNCaP cells after mRNA transcription silencing for Srxn1. The levels of reduced and oxidized peroxiredoxins after Srxn1 silencing will also be investigated. These results will contribute to a better understanding of the role of oxidative stress and Srxn in the PCa, revealing if this enzyme can be a therapeutic target for PCa treatment. (AU)