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Metformin induces resistance of cancer cells to the proteasome inhibitor bortezomib.
Biomolecules 12:756 (2022)
The anti-diabetic drug metformin is currently tested for the treatment of hematological and solid cancers. Proteasome inhibitors, e.g., Bortezomib, are approved for the treatment of multiple myeloma and mantle cell lymphoma but are also studied for lung cancer therapy. We here analyzed the interaction of the two drugs in two cell lines, namely the mantle cell lymphoma Jeko-1 and the non-small-cell lung cancer (NSCLC) H1299 cells, using proliferation and survival assays, native-gel analysis for proteasome activity and assembly, and expression analysis of proteasome assembly factors. Our results demonstrate that metformin treatment induces resistance of cancer cells to the proteasome inhibitor Bortezomib by impairing the activity and assembly of the 26S proteasome complexes. These effects of metformin on proteasome inhibitor sensitivity in cancer cells are of potential relevance for patients that receive proteasome inhibitor therapy.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
26s Proteasome ; Metformin ; Proteasome Activity ; Proteasome Inhibitor ; Resistance
ISSN (print) / ISBN
2218-273X
e-ISSN
2218-273X
Journal
Biomolecules
Quellenangaben
Volume: 12,
Issue: 6,
Article Number: 756
Publisher
MDPI
Publishing Place
Basel
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Lung Health and Immunity (LHI)