Stattic and metformin inhibit brain tumor initiating cells by reducing STAT3-phosphorylation

摘要: // Verena Leidgens 1 , Judith Proske 1, * Lisa Rauer Sylvia Moeckel Kathrin Renner 2 Ulrich Bogdahn Markus J. Riemenschneider 3 Martin Proescholdt 4 Arabel Vollmann-Zwerenz Peter Hau Corinna Seliger Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, Germany Internal Medicine III, Neuropathology, Regensburg Hospital, Neurosurgery, These authors have contributed equally to this work Correspondence to: Seliger, email: corinna.seliger@klinik.uni-regensburg.de Keywords: glioma, BTIC, STAT3, Stattic, metformin Received: August 20, 2016      Accepted: November 21, Published: December 24, 2016 ABSTRACT Glioblastoma (GBM) is the most common malignant type primary brain tumor associated with a devastating prognosis. Signal transducer activator transcription number (STAT3) an important pathogenic factor in GBM can be specifically inhibited Stattic. Metformin inhibits cell proliferation migration. Evidence from other models suggests that but there no specific data on initiating cells (BTICs). We explored migration 7 BTICs their differentiated counterparts (TCs) after treatment or combination thereof. Invasion was measured situ organotypic slice cultures. Protein expression phosphorylated total as well AMPK mTOR signaling were using Western blot. To determine functional relevance STAT3 inhibition by Stattic metformin, we performed stable knock-in selected BTICs. Inhibition reduced all BTICs, only out TCs. Migration invasion Treatment STAT3-phosphorylation investigated Combined led significant additive effects BTIC proliferation, not invasion. No TCs could detected. Stable partly attenuated In conclusion, found inhibit unspecific might represent promising new strategy glioblastoma.