Anti-Metastatic Effects of Aprepitant on Glioblastoma Cells: Targeting the Substance P/Neurokinin-1 Pathway.

Glioblastoma (GB) is an aggressive brain tumor characterized by rapid proliferation, invasion, and resistance to therapy. The substance P (SP)/neurokinin-1 receptor (NK-1R) pathway contributes to GB progression by promoting angiogenesis, inflammation, and extracellular matrix remodeling. Aprepitant, an FDA-approved NK-1R antagonist, has shown potential as a therapeutic agent in glioma treatment. This study investigates the anti-metastatic effects of aprepitant on U87-MG glioblastoma cells. Cell viability, migration, and invasion were evaluated using WST-1, real-time cell analysis, and Oris migration assays. Gene and protein expression levels were assessed by RT-PCR, ELISA, and microarray analysis. Aprepitant significantly reduced glioma cell proliferation, migration, and invasion in a dose-dependent manner. It downregulated pro-tumorigenic mediators such as VEGF, NF-kB, TNF-α, IL-6, IL-8, CCL3, CXCL3, and TRIM5, indicating suppression of angiogenesis, inflammation, and chemotaxis pathways. These findings underscore the potent anti-metastatic and anti-angiogenic effects of NK-1R antagonism in glioblastoma and highlight aprepitant as a promising candidate for future in vivo and in ovo therapeutic investigations targeting extracellular matrix (ECM) remodeling, chemotaxis, and angiogenesis.