Chen Kunlun, Tang Hongwei, Zhu Pengfei, Ye Jianwen, Liu Dong, Pu Yansong, Zhang Lei, Zhai Wenlong
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Departments of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China.
J Cancer. 2020 May 18;11(15):4406-4412. doi: 10.7150/jca.40656. eCollection 2020.
As a pro-inflammatory cytokine, Interleukin 17A (IL-17A) plays an important role in pathology of tumor microenvironment and inflammatory diseases. In this study, we intend to investigate the role of IL-17A on the metastasis of gallbladder cancer (GBC) and related mechanisms. The serum levels of IL-17A were associated with node metastasis and advanced stage. We also found the pro-invasion effect of IL-17A on GBC cells. When treated with IL-17A, the protein level of epithelial marker E-cadherin in GBC cells was significantly down-regulated, while the protein level of the mesenchymal phenotype marker vimentin was significantly increased. IL-17A increased the expression of transcription factor slug, the phosphorylation of ERK1/2 and the nuclear translocation of NF-κB/p50 and p65 in a concentration-dependent manner. Pretreatment of cells with U0126 could reverse the nuclear translocation of NF-κB/p50 and p65 and EMT induced by IL-17A. IL-17A promotes gallbladder cancer invasiveness via ERK/NF-κB signal pathway mediated epithelial-to-mesenchymal transition. As a new therapeutic targets and diagnostic marker, IL-17A may play an important role in the treatment of GBC.
作为一种促炎细胞因子，白细胞介素17A（IL-17A）在肿瘤微环境病理和炎症性疾病中发挥着重要作用。在本研究中，我们旨在探讨IL-17A在胆囊癌（GBC）转移中的作用及相关机制。IL-17A的血清水平与淋巴结转移和晚期阶段相关。我们还发现IL-17A对GBC细胞具有促侵袭作用。用IL-17A处理时，GBC细胞中上皮标志物E-钙黏蛋白的蛋白水平显著下调，而间充质表型标志物波形蛋白的蛋白水平显著升高。IL-17A以浓度依赖性方式增加转录因子slug的表达、ERK1/2的磷酸化以及NF-κB/p50和p65的核转位。用U0126预处理细胞可逆转IL-17A诱导的NF-κB/p50和p65的核转位以及上皮-间质转化（EMT）。IL-17A通过ERK/NF-κB信号通路介导的上皮-间质转化促进胆囊癌侵袭。作为一种新的治疗靶点和诊断标志物，IL-17A可能在GBC的治疗中发挥重要作用。
