NIH Research Festival
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FAES Terrace
NINDS
CANCER-21
Introduction Glioblastoma (GBM) is the most common and uniformly fatal malignant brain tumor. Despite improved understanding of its pathogenesis, survivorship rates remain poor, underscoring the need for novel anti-tumor strategies. Propranolol is a beta-1/beta-2 adrenergic-receptor (BAR/BAR2) antagonist used for treatment of hypertension. Propranolol was discovered to have anti-tumor effects in infantile hemangiomas, thought to be due to inverse-agonism of BARs leading to decreased intracellular levels of cAMP. Preclinical studies suggest broad anti-tumor activity of propranolol against other solid tumors. We investigated whether propranolol may have a role in the treatment of GBM. Methods Four GBM cell lines (U251/GL261/S635 and 9L) were cultured and treated with propranolol. Viability assays, QT-PCR, flow-cytometry, migration assays and western blot analysis were performed using clinically relevant concentrations of propranolol. RNAi was used to determine the dependency of propranolol anti-tumor activity on BAR1 and BAR2 expression. Results Treatment with propranolol reduced GBM viability with an IC50 of 100uM 24-hours post-exposure. Treated cells demonstrated a 6-fold reduction in migratory capacity and increased rates of apoptosis (p
Scientific Focus Area: Cancer Biology
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