Analysis of the expression and inhibition of indoleamine 2,3-dioxygenase (IDO) in the epithelial-mesenchymal transition in bladder cancer

Abstract

Bladder cancer (CB) is the seventh most common cancer in men, noting that noninvasive tumors account for the largest number of cases. Transurethral resection of the bladder tumor (RRTV) associated with Bacilo Calmette-Guérin (BCG) immunotherapy is the most effective treatment and prophylaxis for non-muscle invasive tumors. Treatment with BCG is considered the best therapy, however, approximately 30 to 40% of patients do not respond to this therapy, which may favor the progression of the disease to invasive forms. The use of BCG induces the release of interferon-gamma, an indoleamine-2,3-dioxygenase (IDO) inducer, and IDO is likely to be related to the events triggered by this therapy. IDO, expressed in the placenta and lymphoid organs, plays an immunomodulatory role, which guarantees the tumor escape in several types of cancer. It is known that in the intensification of the epithelial-mesenchymal transition (TEM) mediated by TGF-beta, there is a change in the IDO, the objective of this work is to analyze the expression of these two markers, correlating them with the TEM markers with and without treatment with BCG. In addition, to verify if inhibition of IDO influences TEM in BC with and without BCG treatment. The orthotopic murine CB model will be used. Tumor samples will be collected for immunohistochemical evaluation of the expression of IDO, TGF-beta and TEM markers, as well as by means of real-time PCR. Identifying the participation of IDO in TEM, as well as the pathophysiology of CB, may help the development of new prognostic, diagnostic and therapeutic tools.