Amentoflavone Effectively Blocked the Tumor Progression of Glioblastoma via Suppression of ERK/NF-κB Signaling Pathway

Abstract

Glioblastoma is the most common primary malignant tumor of the central nervous system, with an annual incidence of 5.26 per 100000 people. The clinical outcome of standard therapy and the survival rate remain poor; therefore, there is an unmet need for a new strategy to treat this lethal disease. Although amentoflavone was known to have anticancer potential in various types of cancers, its antiglioblastoma ability and mechanism remain unrecognized. We demonstrated that amentoflavone may suppress glioblastoma invasion and migration by transwell assay. Moreover, we established NF-[Formula: see text]B reporter gene system and used that for verifying NF-[Formula: see text]B inhibition efficacy of amentoflavone on in vitro and in vivo studies. Here, we indicated that amentoflavone not only diminished NF-[Formula: see text]B activation, but also reduced NF-[Formula: see text]B-mediated downstream oncogenes expression, such as MMP-2, MMP-9, XIAP, cyclinD1 and VEGF, which was elucidated by Western blot and immunohistochemistry (IHC). Tumor growth inhibition and NF-[Formula: see text]B reduction was found in the amentoflavone treatment group, which was revealed by the glioblastoma-bearing animal model. In this study, we also used ERK inhibitor and NF-[Formula: see text]B inhibitor (QNZ) to confirm whether the beneficial result of amentoflavone on glioblastoma was mainly regulated by blockage of ERK/NF-[Formula: see text]B signaling. In summary, ERK/NF-[Formula: see text]B signaling pathway has a role in the inhibition of tumor growth by amentoflavone in glioblastoma.