Department of General Surgery, Center for Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
Department of General Surgery, Center for Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
Biochem Biophys Res Commun. 2018 May 5;499(2):273-278. doi: 10.1016/j.bbrc.2018.03.144. Epub 2018 Mar 24.
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.
慢性炎症与癌症发展的所有阶段都有关联。此外，慢性炎症产生的促炎微环境被认为是癌症的一个重要组成部分。白细胞介素-23（IL-23）是一种通用的促炎因子；并参与胃癌（GC）中的肿瘤相关炎症。然而，IL-23 对 GC 细胞的直接作用很少有报道。本研究旨在阐明 IL-23 在调节 GC 进展中的直接作用，并确定其潜在机制。在这项研究中，通过免疫组织化学或免疫荧光法观察到 GC 组织和细胞系中存在 IL-23R 的阳性表达。在 Western blot 中，GC 组织中 IL-23R 的表达高于相邻正常组织。此外，IL-23R 阳性 GC 组织与较大的肿瘤大小、较差的 T 分期和临床分期密切相关。通过进行体外实验，我们发现 IL-23 与其受体结合促进 BGC-823 细胞在体外的迁移和侵袭。此外，IL-23 诱导 BGC-823 细胞中 STAT3 的激活和上皮间质转化（EMT）。在 BGC-823 细胞中敲低 STAT3 减弱了 IL-23 对 EMT 和细胞迁移和侵袭的影响。综上所述，我们的研究首次证明了 IL-23R 在人 GC 组织和细胞系中的阳性表达。IL-23 与其受体结合通过 STAT3 信号通路诱导 EMT 促进 GC 细胞的迁移和侵袭。这项工作为 IL-23 在 GC 进展中的致癌作用提供了一个新的机制。
