Effects of P-MAPA and TNP-470 in the Toll-like receptors signaling pathway in rats with chemically induced proliferative prostate injuries

Abstract

Compounds that act as agonists for Toll-like receptors (TLRs) are considered promising candidates for drug development against cancer, including bladder cancer non-muscle invasive (BCNMI). In this context, the alternative treatments that reduce rates of recurrence, progression, and its impact on clinical outcomes of patients with BCNMI the combination of immunotherapy with P-MAP and inhibition of angiogenesis (TNP-470) can open a new therapeutic approach for this type of tumor. Thus, the main objectives of this study will be to characterize and compare the morphological and molecular effects of the anti-angiogenic therapy associated with the P-MAPA immunotherapy in the treatment of prostatic lesions chemically induced and establish possible action mechanisms of these therapies involving inductors and repairers factors of cellular damage. Fischer 344 female rats (25 animals) will be used. These animals, 5 rats will be used as a Control group (Group 1) and will receive 5 mL/Kg of 0.9% physiological saline 3 times a week for 30 days and 20 rats will undergo chemical induction through a diary subcutaneous dose of 100 mg/Kg of testosterone cypionate with subsequent inoculation (under anesthesia) of N-methyl-N-nitrosurea (MNU, 15mg/Kg) in the capsule of the prostate ventral lobe in every 15 days totalizing 2 doses. A week after the last dose will be given subcutaneous injections of testosterone cypionate in alternate days for 120 days. The 20 chemically induced animals will be divided into four groups with 5 animals in each and these groups will receive the following subcutaneous injections 3 times a week for 30 days: MNU group (Prostatic injuries - Group 2): similar to the group 1; MNU+P-MAPA group (Group3): will receive 5mg/Kg of P-MAPA; MNU+TNP-470 group (Group 4):will receive 15mg/Kg of TNP-470; MNU+P-MAPA+TNP-470 group (Group 5): similar to the groups 3 and 4. After the sacrifice, samples of the prostatic ventral lobe of the 25 animals will be collected for histopathological analysis, immunohistochemistry, and Western Blotting. (AU)