The Effects of Dexamethasone on Mitogen Activated Protein Kinase-14 Signaling in Diffuse Intrinsic Pontine Glioma (DIPG) Cells

Objective: Determine the effects of dexamethasone (DEX) on diffuse intrinsic pontine glioma (DIPG) cell behavior. Background: Patients with DIPG routinely receive DEX to treat vasogenic edema, but the direct effects on tumor growth and sensitivity to other therapies are unknown. Previous studies on glioblastoma cell lines have suggested that DEX interferes with nuclear translocation of p38α mitogen activated protein kinase-14 (MAPK-14), which may be required for cytokine production, cell mobility, and invasion, in addition to a metabolic shift from glycolysis to the pentose phosphate pathway. We tested the hypothesis that DEX prevents nuclear translocation of MAPK-14 in DIPG, resulting in metabolic reprogramming and decreased cell survival, migration, and colony formation. Design/Methods: We used immunocytochemistry to measure the nuclear translocation of total and phosphorylated MAPK-14 in cultured SU-DIPG-IV cells following treatment with DEX or vehicle. We also treated cells with DEX, with or without the clinically relevant chemotherapies panobinostat and imatinib on logarithmic dose curves, and measured proliferation rate, viability and apoptosis with combined assays of trypan blue exclusion and caspase 3/7 activation. Results: Treatment with DEX reduced nuclear localization of phosphorylated MAPK-14 in DIPG cells, but did not affect basal or chemotherapy-inhibited rates of cell proliferation, viability or apoptosis. Conclusions: DEX, a commonly prescribed medication for DIPG patients, decreased nuclear localization of phosphorylated MAPK-14 but had no apparent effects on basal or chemotherapy-inhibited rates of cell proliferation, viability or apoptosis. We are currently exploring the effects of DEX and MAPK-14 signaling on cell metabolism, migration, and colony formation. Disclosure: Dr. Vinson has nothing to disclose. Dr. Chowdhury has nothing to disclose. Dr. Waker has nothing to disclose. Dr. Keoni has nothing to disclose. Dr. Set has nothing to disclose. Dr. Lober has nothing to disclose.