The eIF4A Inhibitor Silvestrol Blocks the Growth of Human Glioblastoma Cells by Inhibiting AKT/mTOR and ERK1/2 Signaling Pathway
Wei Zhang, Pian Gong, Qi Tian, Shoumeng Han, Jianfeng Wang, Peibang He, Yujia Guo, Guijun Wang, Qianxue Chen, Jie Huang, Mingchang Li
Abstract
The most frequently identified central nervous system tumor in adults is glioblastoma multiforme (GBM). GBM prognosis remains poor despite multimodal treatment, i.e., surgery and radiation therapy with concurrent temozolomide-based chemotherapy. Silvestrol, an eIF4A inhibitor, has been demonstrated to be able to kill tumor cells in previous studies. In this study, it was found that silvestrol considerably attenuated the proliferative potential of U251 and U87 glioma cells and reduced expression of cyclin D1. In addition, silvestrol reduced the level of ERK1/2 and decreased the levels of AKT phosphorylation. Unfortunately, the effect of silvestrol in inhibiting GBM cells was greatly reduced with hypoxia, and the downregulation in AKT/mTOR and ERK1/2 were also rescued with an upregulation of HIF1α, which warranted further research. Taken together, silvestrol exerted antitumor effects in GBM cells by inhibiting the AKT/mTOR and ERK1/2 signaling cascades.