Abstract
Chronic inflammation is associated with all stages of cancer development. Moreover, a proinflammatory microenvironment resulted from chronic inflammation is considered to be an essential component of cancer. Interleukin-23 (IL-23) is a general proinflammatory factor; and is involved in tumor-associated inflammation in gastric cancer (GC). However, the direct effect of IL-23 on GC cells has been rarely reported. The aim of the study was to clarify the direct role of IL-23 in regulating GC progression, and to identify the underlying mechanism. In this study, Positive expression of IL-23R was observed in GC tissues and cell lines by using immunohistochemistry or immunofluorescence. In western blots, the expression of IL-23R was higher in GC tissues compared with adjacent normal tissues. Furthermore, IL-23R positive GC tissues were closely related with larger tumor size and worse T stage and clinical stage. By performing in vitro experiments, we found that IL-23 binding to its receptor promoted the migration and invasion of BGC-823 cells in vitro. Moreover, IL-23 induced the activation of STAT3 and epithelial-to-mesenchymal transition (EMT) in BGC-823 cells. Knocking down STAT3 in BGC-823 cells attenuated the effect of IL-23 on EMT and cell migration and invasion. Taken together, our study has firstly demonstrated the positive expression of IL-23R in human GC tissues and cell lines. IL-23 binding to its receptor promotes the migration and invasion of GC cells by inducing EMT through the STAT3 signaling pathway. This work provides a new mechanism for the oncogenic role of IL-23 on GC progression.