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Metformin Confers Sensitisation to Syrosingopine in Multiple Myeloma Cells by Metabolic Blockage and Inhibition of Protein Synthesis by Arne Van der Vreken; Inge Oudaert; Gamze Ates; Sylvia Faict; Philip Vlummens; Hatice Satilmis; Rong Fan; Anke Maes; Ann Massie; Kim De Veirman; Elke De Bruyne; Karin Vanderkerken; Eline Menu is a Medicine article available to read on EtoBox.

What is Metformin Confers Sensitisation to Syrosingopine in Multiple Myeloma Cells by Metabolic Blockage and Inhibition of Protein Synthesis about?

Multiple Myeloma (MM) remains an incurable haematological malignancy despite substantial advances in therapy. The hypoxic bone marrow induces metabolic rewiring in MM cells contributing to survival and drug resistance. Therefore, targeting metabolic pathways may offer an alternative treatment option. In this study, we re-purpose two FDA-approved drugs, syrosingopine and metformin. Syrosingopine was used as a dual inhibitor of monocarboxylate transporter 1 and 4 (MCT1/4) and metformin as an inhibitor for oxidative phosphorylation (OXPHOS). Anti-tumour effects were evaluated for single agents and in combination therapy. Survival and expression data for MCT1/MCT4 were obtained from the TT2, Mulligan and MMRF-cohort. Cell death, viability and proliferation were measured using Annexin V/7-AAD, CellTiterGlo and BrdU, respectively. Metabolic effects were assessed using Seahorse Glycolytic Rate assays and LactateGlo assays. Differential protein expression was determined using western blotting and the SUnSET method was implemented to quantify protein synthesis. Finally, the syngeneic 5T33MMvv model was used for in vivo analysis. High level expression of MCT1 and MCT4 both correlated with a

Who reads Metformin Confers Sensitisation to Syrosingopine in Multiple Myeloma Cells by Metabolic Blockage and Inhibition of Protein Synthesis?

Author

Arne Van der Vreken; Inge Oudaert; Gamze Ates; Sylvia Faict; Philip Vlummens; Hatice Satilmis; Rong Fan; Anke Maes; Ann Massie; Kim De Veirman; Elke De Bruyne; Karin Vanderkerken; Eline Menu

Publisher

Wiley

Published

2023

Language

EN

Field

Medicine (Health Sciences)