4. Nitric oxide inhibition controls local and distant invasive bladder tumor disease, reducing chronic inflammation and increasing the infiltration of cytotoxic immune cells

CAROLINA IGLESIAS ; DENISE BELGOROSKY; BELÉN AMATO ; YANINA LANGLE ; ANA MARIA EIJAN

Congreso; Reunion Anual de Sociedades de Biociencias; 2023

Bladder cancer (BC) is classified into non-invasive (NMI) and muscle invasive (MI) tumors. Inducible nitric oxide synthase (iNOS) is expressed in more than 50% of patients with BC and produces high levels of nitric oxide (NO). iNOS is a poor prognosis marker in BC, associated with invasion and early recurrence. Previously, using a murine BC model that express iNOS we demonstrated that NO inhibition with 0.5 g/L of L-NAME reduced subcutaneous tumor growth.Objective: to evaluate the bladder tumor growth, the immune cell profile and the spontaneous metastasis develop in a MI murine BC model that express iNOS. Methods: Bladder tumor weight and the lung incidence of metastasis were measured in tumor bearing mice (TBM) inoculated orthotopically with MB49-I (MI BC cells) and treated with L-NAME (0.5 and 1 g/L in drinking water). Bladder CD8+, NK and Treg were evaluated by flow cytometry and iNOS and TGF-β expression by qPCR.Results: L-NAME treatment at doses of 0.5 and 1 g/L similarly reduced the orthotopic tumor growth (p