Affiliation:
1. Department of Structural and Functional Biology, State University of Campinas (UNICAMP), Campinas, SP
Abstract
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. 50mg/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.
Publisher
Research Square Platform LLC
Reference53 articles.
1. Vimentin as a potential molecular target in cancer therapy Or Vimentin, an overview and its potential as a molecular target for cancer therapy;SHULIN ARUNS;Cell Mol Life Sci v,2011
2. BARRON DA, ROWLEY, David R (2012) The reactive stroma microenvironment and prostate cancer progression. Endocrine-related cancer, v. 19, n. 6, p. R187-R204,
3. Oxidative stress and antioxidant status in prostate cancer patients: relation to Gleason score, treatment and bone metastasis;Vanessa BATTISTI;Biomed Pharmacother,2011
4. The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms;Claes BAVIK;Cancer Res,2006
5. A review of the existing grading schemes and a proposal for a modified grading scheme for prostatic lesions in TRAMP mice. Toxicologic pathology, v. 40, n. 1;Lisa BERMAN-BOOTY,2012