biostudies-literaturePapachristodoulou ANCI NIH HHSNIGMS NIH HHS361-372https://www.ebi.ac.uk/biostudies/studies/S-EPMC10902192biostudies-literatureUnknown85(4)<h4>Background</h4>The antidiabetic drug metformin has known anticancer effects related to its antioxidant activity; however, its clinical benefit for prostate cancer (PCa) has thus far been inconclusive. Here, we investigate whether the efficacy of metformin in PCa is related to the expression status of NKX3.1, a prostate-specific homeobox gene that functions in mitochondria to protect the prostate from aberrant oxidative stress.<h4>Objective</h4>To investigate the relationship of NKX3.1 expression and metformin efficacy in PCa.<h4>Design, setting, and participants</h4>Functional studies were performed in vivo and in vitro in genetically engineered mouse models and human LNCaP cells, and organotypic cultures having normal or reduced/absent levels of NKX3.1. Correlative studies were perforEuropean urologyMetformin Overcomes the Consequences of NKX3.1 Loss to Suppress Prostate Cancer Progression.PMC10902192P20 GM103446R01 CA233176P50 CA211024P01 CA265768R01 CA173481K99 CA276713P30 CA013696De Castro GJHeidegger IAbate-Shen CKlocker HSchafer GZheng TVirk RKPapachristodoulou AKim JYLoda MDutta AMcKiernan JMBenson MCLaplaca CHibshoosh HDi Bernardo MRubin MAPicech FfalseMetformin Overcomes the Consequences of NKX3.1 Loss to Suppress Prostate Cancer Progression.<h4>Background</h4>The antidiabetic drug metformin has known anticancer effects related to its antioxidant activity; however, its clinical benefit for prostate cancer (PCa) has thus far been inconclusive. Here, we investigate whether the efficacy of metformin in PCa is related to the expression status of NKX3.1, a prostate-specific homeobox gene that functions in mitochondria to protect the prostate from aberrant oxidative stress.<h4>Objective</h4>To investigate the relationship of NKX3.1 expression and metformin efficacy in PCa.<h4>Design, setting, and participants</h4>Functional studies were performed in vivo and in vitro in genetically engineered mouse models and human LNCaP cells, and organotypic cultures having normal or reduced/absent levels of NKX3.1. Correlative studies were perfor2024-01-01T00:00:00Z2024 Apr2026-06-02T18:10:42.494Z2025-07-11T03:04:07.851ZS-EPMC109021923765996210.1016/j.eururo.2023.07.016