Creation of an apoptin-derived peptide that interacts with SH3 domains and inhibits glioma cell migration and invasion.

Abstract

Glioblastoma multiforme (GBM) is an aggressive tumor of the central nervous system characterized by high rates of recurrence, morbidity, and mortality. This study investigated the antitumor effects of an apoptin-derived peptide (ADP) on glioma cells and explored the underlying mechanisms. The U251, U87, and C6 glioma cell lines were used in the present study, and the expression of p-Akt, Akt, and MMP-9 was determined through Western blotting, quantitative real-time PCR, and hematoxylin and eosin (HE) staining. Tumor growth was evaluated by magnetic resonance imaging, and cell viability was assessed through an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay. Glioma cell metastasis was evaluated using transwell migration, invasion, and scratch-wound assays. An ADP was designed and synthesized based on the results of a domain-based analysis of the structure of apoptin. The ADP inhibited glioma cell viability, invasion and migration, and treatment with the synthesized ADP led to downregulation of p-Akt and MMP-9 and inhibited MMP-9 translation. The ADP also inhibited glioma invasion and migration in vivo, and HE staining showed decreases in the satellite-like invasion of cell masses and apoptotic cell populations after treatment with the ADP. Our findings demonstrate that treatment with an ADP can suppress glioma cell migration and invasion via the PI3K/Akt/MMP-9 signaling pathway and provide a new platform for the development of drugs for treating glioma.