Indatraline inhibits Rho- and calcium-mediated glioblastoma cell motility and angiogenesis

摘要: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor of central nervous system (CNS). As an attempt to identify drugs for GBM therapeutics, phenotypic assays were used screen 1000 chemicals from a clinical compound library. subtypes exhibited different capabilities induce angiogenesis when cultured on Matrigel; proneural cells migrated formed tube-like structure without endothelial cells. Among compounds screened, indatraline, nonselective monoamine transporter inhibitor, suppressed these morphological changes; it dose dependently inhibited cell spreading, migration, in vitro/in vivo tube formation. In addition intracellular calcium concentration, indatraline increased level Rho GTPase its activity. Moreover, downregulated angiogenesis-related genes such as IGFBP2, PTN, VEGFA, PDGFRA, VEGFR well nestin, stem marker. These findings collectively suggest that activation suppression factors mediate antiangiogenic activity culture.