Anti-inflammatory therapies in TRAMP mice: delay in PCa progression

• Published in: Endocrine-related cancer Vol. 23; no. 4; pp. 235 - 250
• Main Authors: Kido, Larissa Akemi, Montico, Fabio, Sauce, Rafael, Macedo, Aline Barbosa, Minatel, Elaine, Costa, Débora Barbosa Vendramini, de Carvalho, João Ernesto, Pilli, Ronaldo Aloise, Cagnon, Valeria Helena Alves
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.04.2016
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma - prevention & control; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Celecoxib - pharmacology; Celecoxib - therapeutic use; Cyclooxygenase 2 - metabolism; Disease Models, Animal; Interleukin-1beta - blood; Male; Mice; Mice, Transgenic; NF-kappa B - metabolism; Proliferating Cell Nuclear Antigen - metabolism; Prostate - drug effects; Prostate - metabolism; Prostate - pathology; Prostatic Neoplasms - blood; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - prevention & control; Pyrones - pharmacology; Pyrones - therapeutic use; Receptor, IGF Type 1 - metabolism; STAT3 Transcription Factor - metabolism; Tumor Necrosis Factor-alpha - blood; anti-inflammatory therapies; goniothalamin; prostate cancer; TRAMP; inflammation
• ISSN: 1351-0088; 1479-6821
• DOI: 10.1530/ERC-15-0540

Abstract The aim of this study was to characterize the structural and molecular biology as well as evaluate the immediate and late responses of prostatic cancer in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model after treatment with goniothalamin (GTN) and celecoxib. The treated mice received GTN (150 mg/kg, gavage) or celecoxib (10 mg/kg, gavage) from 8 to 12 weeks of age. They were killed at different ages: the immediate-response groups at 12 weeks and the late-response groups at 22 weeks. The ventral prostate was collected for light microscopy, immunohistochemistry, western blotting, TUNEL, and ELISA. Morphological analyses indicated that GTN treatment delayed the progression of prostatic adenocarcinoma, leading to a significant decrease of prostatic lesion frequency in both experimental period responses to this treatment, mainly high-grade prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma. Also, the celecoxib treatment showed a particular decrease in the proliferative processes (PCNA) in both the experimental periods. Despite celecoxib diminishing the COX2 and IGFR1 levels, GTN presented higher action spectrum considering the decrease of a greater molecular number involved in the proliferative and inflammatory processes in prostatic cancer. Goniothalamin attenuated the pro-inflammatory response in TRAMP prostatic microenvironment, delaying prostate cancer (PCa) progression. Celecoxib treatment was efficient in the regulation of COX2 in the TRAMP mice, mainly in the advanced disease grade. Finally, we concluded that inflammatory process control in early grades of PCa was crucial for the downregulation of the signaling pathways involved in the proliferative processes in advanced cancer grades.