{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T20:12:52Z","timestamp":1771359172294,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T00:00:00Z","timestamp":1653696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HELMOLTZ CENTER MUNICH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biom12060756","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T08:50:51Z","timestamp":1653814251000},"page":"756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Metformin Induces Resistance of Cancer Cells to the Proteasome Inhibitor Bortezomib"],"prefix":"10.3390","volume":"12","author":[{"given":"Camille","family":"Schlesser","sequence":"first","affiliation":[{"name":"Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Ludwig-Maximilians University, Max-Lebsche Platz 31, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Meul","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Ludwig-Maximilians University, Max-Lebsche Platz 31, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9215-6461","authenticated-orcid":false,"given":"Georgios","family":"Stathopoulos","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Ludwig-Maximilians University, Max-Lebsche Platz 31, 81377 Munich, Germany"},{"name":"Member of the German Center for Lung Research (DZL), 35392 Gie\u00dfen, Germany"},{"name":"Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3678-7995","authenticated-orcid":false,"given":"Silke","family":"Meiners","sequence":"additional","affiliation":[{"name":"Comprehensive Pneumology Center (CPC), Helmholtz Center Munich, Ludwig-Maximilians University, Max-Lebsche Platz 31, 81377 Munich, Germany"},{"name":"Research Center Borstel\/Leibniz Lung Center, Parkallee 1-40, 23845 Borstel, Germany"},{"name":"Airway Research Center North (ARCN), German Center for Lung Research (DZL), 23845 S\u00fclfeld, Germany"},{"name":"Institute of Experimental Medicine, Christian-Albrechts University Kiel, 24118 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","article-title":"Metformin: From Mechanisms of Action to Therapies","volume":"20","author":"Foretz","year":"2014","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.molcel.2017.05.032","article-title":"AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance","volume":"66","author":"Garcia","year":"2017","journal-title":"Mol. 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