ArticleNan fang yi ke da xue xue bao = Journal of Southern Medical University2023
[Metformin inhibits self-renewal of colorectal cancer stem cells by inhibiting mitochondrial oxidative phosphorylation].
Article in Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Metabolic reprogramming and plasticity of cancer stem cells.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial DNA Mutations in Colorectal Cancer Stem Cells: Implications for Tumor Dynamics and Therapeutic Strategies.Current medicinal chemistry · 2026Review
- Research Progress on the Use of Metformin in Leukemia Treatment.Current treatment options in oncology · 2024Review
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo investigate the mechanism of metformin for inhibiting self-renewal of colorectal cancer stem cells (CSCs).
methodsCSCs were sorted from Wnt reporter- transfected colorectal cancer patient-derived organoids (PDOs) by fluorescence-activated cell sorting (FACS) and treated with metformin. The changes in self-renewal of the cells were assessed using sphere formation, colony formation and limiting dilution assays. The mRNA expressions of genes related with stemness and differentiation and Wnt target genes was detected by qRT-PCR. Wnt activity was assessed using flow cytometry in the CSCs. Seahorse analysis was used to evaluate cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) after metformin treatment. Mitochondrial membrane potential levels were detected with TMRE staining, and reactive oxygen species (ROS) levels were detected using MitoSOX staining. Galactose (10 mmol/L), metformin (10 μmol/L), NAC (5 mmol/L), and galactose+metformin were used to modulate ROS levels in the CSCs, and sphere-formation assay and flow cytometry were used to assess the changes in self- renewal capacity and Wnt activity. The effect of lentiviral transfection of yeast NADH dehydrogenase NDI1 on TMRE staining, MitoSOX staining and Wnt activity in the CSCs were analyzed with flow cytometry.
resultsMetformin significantly decreased the capacities of CSCs to form spheres, colonies and xenografts and reduced Wnt activity in the cells (
conclusionMetformin reduces mitochondrial oxidative phosphorylation and ROS levels by inhibiting mitochondrial complex Ⅰ, thereby suppressing Wnt signaling pathway to reduce selfrenewal ability of colorectal CSCs.
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