IL‐17A promotes cell migration and invasion of glioblastoma cells via activation of PI3K/AKT signalling pathway

摘要

Glioblastomas (GBMs) are the most common of both benign and malignant primary brain tumours, in which the inflammatory and immunologic abnormalities are involved. Interleukin‐17A (IL‐17A) plays an important role in various inflammatory diseases and cancers. Several recent studies revealed that the expression of IL‐17A was overexpressed in human GBMs tissue. However, the accurate role of IL‐17A in GBMs remains unclear. In this study, we aimed to explore the effect of IL‐17A on cell migration and invasion of GBMs and the mechanism by which the effects occurred. We found that exogenous IL‐17A promoted significantly cell migration and invasion abilities in two GBMs cell lines (U87MG and U251) in a time‐dependent manner. In addition, the protein expressions of PI3K, Akt and MMP‐2/9 were increased in the GBMs cells challenged by IL‐17A. Furthermore, a tight junction protein ZO‐1 was down‐regulated but Twist and Bmi1 were up‐regulated. Treatment with a style="fixed-case">PI3K inhibitor ( style="fixed-case">LY294002) significantly reduced the abilities of both migration and invasion in U87 style="fixed-case">MG and U251 cells. style="fixed-case">LY294002 treatment also attenuated the style="fixed-case">IL‐17A causing increases of protein levels of style="fixed-case">PI3K, style="fixed-case">AKT, style="fixed-case"> MMP‐2/9, Twist and the decreases of protein level of style="fixed-case">ZO‐1 in the U87 style="fixed-case">MG and U251 cells. Taken together, we concluded that style="fixed-case">IL‐17A promotes the style="fixed-case">GBM cells migration and invasion via style="fixed-case">PI3K/ style="fixed-case">AKT signalling pathway. style="fixed-case">IL‐17A and its related signalling pathways may be potential therapeutic targets for style="fixed-case">GBM.