Abstract
Prostate cancer (PCa) is the second cause of cancer death among men worldwide. Several processes are involved in the development and progression of PCa such as angiogenesis, inflammation and oxidative stress. The present study investigated the effect of short- or long-term Tempol treatment at different stages of prostate adenocarcinoma progression, focusing on angiogenic, proliferative, and stromal remodeling processes in TRAMP mice. The dorsolateral lobe of the prostate of TRAMP mice were evaluated at two different stages of PCa progression; early and late stages. Early stage was again divided into, short- or long-term. 50 mg/kg Tempol dose was administered orally. The results demonstrated that Tempol mitigated the prostate histopathological lesion progressions in the TRAMP mice in all treated groups. However, Tempol increased molecules involved in the angiogenic process such as CD31 and VEGFR2 relative frequencies, particularly in long-term treatment. In addition, Tempol upregulated molecule levels involved in angiogenesis and stromal remodeling process VEGF, TGF-β1, VE-cadherin and vimentin, particularly, in T8-16 group. Thus, it was concluded that Tempol treatment delayed prostatic lesion progression in the dorsolateral lobe of the TRAMP mice. However, Tempol also led to pro-angiogenic effects and glandular stromal microenvironment imbalance, especially, in the long-term treatment.
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Acknowledgements
Thanks the Multidisciplinary Center for Biological Investigation on Laboratory Animal Science (CEMIB)/UNICAMP.
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This study was supported by the Coordination for the improvement of higher Education Personnel – Brasil (CAPES) – Finance Code 001 and São Paulo Research Foundation – FAPESP (2018/21647-6 and 2021/02108-0).
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CVHA and SFR: These authors proposed the main manuscript idea and wrote the manuscript text. And also developed the experiment. RIMU: She also took part the experimental tecnics. SFR: He prepared figures. All authors reviewed the manuscript and wrote some part of the text.
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Santos, F.R., Rossetto, I.M.U., Montico, F. et al. Differential tempol effects in prostatic cancer: angiogenesis and short- and long-term treatments. J Mol Histol (2024). https://doi.org/10.1007/s10735-024-10187-4
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DOI: https://doi.org/10.1007/s10735-024-10187-4