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

Abstract

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 PI3K inhibitor (LY294002) significantly reduced the abilities of both migration and invasion in U87MG and U251 cells. LY294002 treatment also attenuated the IL-17A causing increases of protein levels of PI3K, AKT, MMP-2/9, Twist and the decreases of protein level of ZO-1 in the U87MG and U251 cells. Taken together, we concluded that IL-17A promotes the GBM cells migration and invasion via PI3K/AKT signalling pathway. IL-17A and its related signalling pathways may be potential therapeutic targets for GBM.