THE EFFECT OF STABILIZING OR INHIBITING HYPOXIA-INDUCIBLE FACTORS ON THE TREATMENT OF GLIOBLASTOMA CELLS WITH METFORMIN

Metformin has demonstrated anti-proliferative effects in various cancer entities, including glioblastoma, the most prevalent primary brain tumors. Its main effects lead to inhibition of mTORC1 and therefore to lower expression of hypoxia-inducible factors (HIF), key mediators of cellular adaptation to hypoxic conditions. Although HIF appear to be a negative prognostic factor in glioblastoma, HIF stabilization may also enhance the antitumor immune response. In particular, the role of HIF2α in metformin's anti-proliferative effect on glioblastoma cells as well as its connection to primary cilia, specialized sensory organelles often referred to as the “antenna of the cell”, remains to be investigated.
To gain further insight into these interactions, glioblastoma cells from two established cell lines (RG2 and U87) will be treated with metformin in combination with either a HIF stabilizer or a HIF-2α inhibitor. Subsequent analyzes on RNA expression via qPCR and protein accumulation via Western Blot will focus on cellular functions, paying special attention to HIF-related signaling pathways. Functional outcomes, including cell viability and migratory capacity, will be evaluated using LDH release assays and scratch assays. Primary cilia morphology and abundance will be examined by immunofluorescence microscopy.
This study aims to elucidate the role of hypoxia-inducible factors in metformin-treatment of glioblastoma cells and to determine the cellular consequences of HIF stabilization or inhibition.