Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Haitzmann, T.
Dual inhibition of glycolysis and gluconeogenesis in lung cancer cells and spheroids.
[ Diplomarbeit/Master Thesis (UNI) ] FH Joanneum; 2021. pp.73.
- Autor*innen der Med Uni Graz:
- Haitzmann Theresa
- Betreuer*innen:
- Leithner Katharina
- Altmetrics:
- Abstract:
- Metabolic vulnerabilities of cancer cells are being studied as potential therapeutic targets, because tumor metabolism is reprogrammed and differs from normal cells. Cancer cells rely primarily on glycolysis, but due to their high glucose consumption rates and the inadequate vascular supply in fast-growing tumors, they often experience glucose deprivation. Recently, it has been shown that gluconeogenesis is used as an adaptive response under lack of glucose to maintain biosynthetic pathways and proliferation by expressing phosphoenolpyruvate carboxykinase (PEPCK). However, the effect of suppressing glycolysis and gluconeogenesis simultaneously in cancer cells has not been studied. In this master thesis, the impact of dual inhibition of glycolysis and gluconeogenesis on lung cancer cells was investigated in vitro. Therefore, the growth rate in 3D lung cancer spheroids and the proliferation rate in 2D cell culture was examined and analyzed for a synergistic effect. 2-deoxyglucose (2-DG) was used for inhibition of glycolysis, and gluconeogenesis was blocked either pharmacologically, by using Axon1165 or through shRNA mediated silencing of PCK2 (mitochondrial isoform of PEPCK). Also, the effect of 2-DG on PCK2 mRNA and protein expression was examined. (...)