Sulfiredoxina: um potencial alvo terapêutico para o câncer de próstata avançado

Abstract

Despite the effectiveness of surgical and anti-androgenic therapies against organ-confined and metastatic prostate cancer (PCa), respectively, new therapeutic approaches are still needed for treatment of advanced metastatic PCa that occasionally becomes resistant to androgen deprivation, chemo and radiation therapies, which are responsible for all deaths related to this disease. Oxidative stress unbalance is involved with cancer development, progression and metastasis, including PCa. Sulfiredoxin, an antioxidant enzyme, has been shown to have elevated expression in the tumorigenic process of different organs. Here, we analyzed the expression of sulfiredoxin in PCa, investigating its potential as a new therapeutic target for PCa. Sulfiredoxin expression was investigated by immunohistochemistry in PCa from transgenic mice conditional knockout for Pten and human prostate cancer and showed an increased expression in undifferentiated adenocarcinoma and high grade Gleason tumors. In the human data base TCGA, 5% of patients with PCa have higher expression of sulfiredoxin and also lower disease free survival rates (P<0,000122). Quantitative PCR showed that tumor cell lines, PC-3 and LNCaP, express higher levels of sulfiredoxin than prostate normal cell line RWPE-1, which are in agreement with results from metadata analysis in the GEO profile from others studies. Our results demonstrate that sulfiredoxin play a role in some subset of PCa, especially in the advanced stages of the tumor. Considering the personalized medicine, our results suggest that inhibition of this enzyme can be an effective strategy of adjuvant treatment to castration-resistant CaP patients with sulfiredoxin upregulation.

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