The use of 1400W, an specific inhibitor of Inducible Nitric Oxide Synthase, in an orthotopic bladder cancer murine model

BELGOROSKY D ; LANGLE YV ; EIJÁN AM

San Pablo

Workshop; Course ? Advances in molecular oncology: translating molecular biology into cancer treatment-. 2nd to 8th february 2013, Sao Paulo, Brazil.; 2013

Fundação de Amparo à Pesquisa do Estado de São Paulo

The use of 1400W, an specific inhibitor of Inducible Nitric Oxide Synthase, in an orthotopic bladder cancer murine model Belgorosky D, Langle YV, Eiján AM Instituto de Oncología Ángel H. Roffo. Avenida San Martin 5481, CABA, Argentina. Nitric-oxide (NO) is a free radical produced by enzymes called NOS. The inducible isoform (iNOS) produces high levels of NO in response to inflammatory stimuli. The expression of iNOS in human bladder tumors is a poor prognostic factor associated with increased invasion and tumor recurrence. We have developed a mouse model of bladder cancer ( Bca) with different degree of invasion that mimics human pathology. Orthotopic Inoculation MB49 cell line develops tumors confined to the bladder epithelium with a low expression of iNOS, whereas MB49-I developed invasive tumors with high expression of the enzyme in the tumor tissue and in not vesical tumoral tissue. Therefore, we analyzed the response of this cell lines to 1400W, a specific pharmacological inhibitor of iNOS, in vitro and in vivo. In vitro, 1400W (5uM) decreased NO production in both cell lines (p