Zhang Jian-Fei, Wang Peng, Yan Yu-Jin, Li Yong, Guan Min-Wu, Yu Jin-Jun, Wang Xin-Dong
Department of Neurosurgery, Affiliated Hospital of School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
Department of Neurosurgery, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu 214002, P.R. China.
Oncol Rep. 2017 Oct;38(4):2033-2042. doi: 10.3892/or.2017.5926. Epub 2017 Aug 25.
As an important member of the interleukin (IL)-1 family, IL‑33 plays a significant role in tumor progression. To explore this, we previously analyzed the association between IL‑33 expression and the prognosis of patients with glioma. However, the function of the IL‑33/ST2 axis in glioma remained unclear. In the present study, immunofluorescent staining results revealed that the expression levels of IL‑33 and ST2 receptor in glioma tissues were higher than those in normal brain tissues. Invasion and migration assays demonstrated that IL‑33 significantly increased glioma cell invasion and migration in vitro. Furthermore, knockdown of ST2 by siRNA attenuated the IL‑33-induced increase in invasion and migration. In addition, ELISA results revealed that IL‑33 upregulated the expression of matrix metalloproteinase (MMP)2 and MMP9. Western blot analysis results indicated that IL‑33 stimulation increased the phosphorylation of nuclear factor-κB (NF-κB) in a time- and dose-dependent manner. Moreover, silencing of the NF-κB pathway by BAY 11‑7082 resulted in the inhibition of IL‑33-induced invasion and migration, as well as the downregulation of MMP2 and MMP9 production. These findings indicate that IL‑33 may be involved in the process of glioma cell invasion and migration by upregulating MMP2 and MMP9 via the ST2-NF-κB signaling pathway. Thus, IL‑33 may be a novel therapeutic target for glioma.
作为白细胞介素（IL）-1家族的重要成员，IL-33在肿瘤进展中发挥着重要作用。为了探究这一点，我们之前分析了IL-33表达与胶质瘤患者预后之间的关联。然而，IL-33/ST2轴在胶质瘤中的功能仍不清楚。在本研究中，免疫荧光染色结果显示，胶质瘤组织中IL-33和ST2受体的表达水平高于正常脑组织。侵袭和迁移实验表明，IL-33在体外显著增加了胶质瘤细胞的侵袭和迁移。此外，通过小干扰RNA（siRNA）敲低ST2可减弱IL-33诱导的侵袭和迁移增加。另外，酶联免疫吸附测定（ELISA）结果显示，IL-33上调了基质金属蛋白酶（MMP）2和MMP9的表达。蛋白质印迹分析结果表明，IL-33刺激以时间和剂量依赖性方式增加了核因子κB（NF-κB）的磷酸化。此外，用BAY 11-7082沉默NF-κB信号通路导致IL-33诱导的侵袭和迁移受到抑制，以及MMP2和MMP9生成的下调。这些发现表明，IL-33可能通过ST2-NF-κB信号通路上调MMP2和MMP9而参与胶质瘤细胞的侵袭和迁移过程。因此，IL-33可能是胶质瘤的一个新的治疗靶点。
