Análise da inibição da enzima indoleamina 2,3 dioxigenase por 1-metil triptofano na indução transição epitélio mesenquimal em células T24 de câncer de bexiga humana

• Autor(a) principal: Brito, Rodrigo Barbosa de Oliveira
• Data de Publicação: 2021
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da Uninove
• Texto Completo: http://bibliotecatede.uninove.br/handle/tede/3328
• topic: transição epitélio mesenquimal; carcinoma de bexiga urinária; indoleamina 2,3 dioxigenase; mesenchymal epithelium transition; urinary bladder carcinoma; indoleamine 2,3 dioxygenase; CIENCIAS DA SAUDE

Bladder cancer stands out for its high relapse capacity and metastatic progression, related to a mesenchymal epithelial transition (EMT). Indoleamine 2,3 dioxygenase (IDO) is an enzyme expressed in several types of tumors, associated with tumor escape, due to its immunological mechanisms. There is evidence that an IDO participates in EMT through TGF-β1. 1-methyl tryptophan (MT), the chemical inhibitor of IDO, potentiates EMT in bladder cancer cells. One possibility is that MT is able to activate the aryl hydrocarbon receptor (AHR), as AHR has been linked in the EMT process in other cancers. The aim of the present study is to analyze the activation of AHR in human bladder carcinoma T24 cells by MT, in order to correlate it with the EMT process. For this, a "silica analysis" of the GSE13507 database correlated to the relative expression of AHR, CYP1A1, CYP1A2 and CYP1B1 was performed. For an “in vitro” analysis how T24 cells will be incubated with TGF-beta1, MT and/or CH223191, an AHR inhibitor. The results "in silico" it was possible to observe high expression of CYP1A1 and CYP1A2 associated with the histological grade, stage and progression of the tumor. In the “in vitro” analysis, the results showed that CH223191 is able to inhibit the activation of the AHR by decreasing the expression of CYP1A1. However, inhibition of AHR activation is unable to prevent EMT triggered by 1MT and TGF-beta1. Although EMT reversal is not observed, we cannot rule out that AHR is related to EMT potentiation triggered by MT, as finding EMT markers requires a combinatorial approach, as well as distinguishing between EMT-associated and non-EMT-associated functions. We conclude that MT is able to activate AHR in bladder cancer, suggesting a metabolic pathway that justifies the potentiating effect of MT on EMT triggered by TGF-beta1.