Overexpression of Indoleamine 2,3-Dioxygenase 1 Promotes Epithelial-Mesenchymal Transition by Activation of the IL-6/STAT3/PD-L1 Pathway in Bladder Cancer

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme in tryptophan metabolism and plays an important role in tumor cell immunosuppression and angiogenesis. The molecular mechanisms of IDO1 and epithelial-mesenchymal transition (EMT) have not been elucidated or studied in bladder cancer. Therefore, the aims of this study were to detect IDO1 expression in bladder cancer tissues and then to investigate the role of IDO1 in bladder cancer cell EMT and malignant phenotypes as well as the underlying molecular mechanisms. By immunohistochemistry, Western blot, and quantitative reverse transcription–polymerase chain reaction experiments, IDO1 was found to be overexpressed in bladder cancer tissues and cell lines compared to the noncancerous ones. In addition, knockdown of IDO1 expression was shown to inhibit bladder cancer cell growth, migration, invasion, and EMT. Furthermore, we demonstrated that IDO1 may promote EMT by activation of the interleukin 6/signal transducer and activator of transcription 3/programmed cell death ligand 1 signaling pathway. Collectively, these data suggest that IDO1 may play an important role in bladder cancer and may be a novel therapeutic target for patients with bladder cancer.