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

Author(s)

Kido, Larissa Akemi ^[1] ; Montico, Fabio ^[1] ; Sauce, Rafael ^[1] ; Macedo, Aline Barbosa ^[1] ; Minatel, Elaine ^[1] ; Vendramini Costa, Debora Barbosa ^{[2, 3]} ; de Carvalho, Joao Ernesto ^{[2, 4]} ; Pilli, Ronaldo Aloise ^[3] ; Alves Cagnon, Valeria Helena ^[1]

Affiliation

^[1] Univ Campinas UNICAMP, Inst Biol, Struct & Cellular Biol Postgrad Program, Dept Struct & Funct Biol, Sao Paulo - Brazil

^[2] Univ Campinas UNICAMP, CPQBA, Chem Biol & Agr Pluridisciplinary Res Ctr, Sao Paulo - Brazil

^[3] Univ Campinas UNICAMP, Inst Chem, Dept Organ Chem, Sao Paulo - Brazil

^[4] Univ Campinas UNICAMP, Fac Pharmaceut Sci, Sao Paulo - Brazil

• Document type: Journal article
• Source: Endocrine-Related Cancer; v. 23, n. 4, p. 235-250, APR 2016.
• Web of Science Citations: 12

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. (AU)

• FAPESP's process: 13/01294-8 - The controversial relationship between inflammation and prostatic lesions: treatment with Celecoxib and Goniothalamin in senile and Tramp mice
• Grantee: Larissa Akemi Kido de Barros
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/23049-5 - Prostatic lesions, inflammation and aging: effects of anti-inflammatory therapies in transgenic adenocarcinoma of the mouse prostate model and in senile FVB mice
• Grantee: Valéria Helena Alves Cagnon Quitete
• Support type: Regular Research Grants