ArticleCell cycle (Georgetown, Tex.)2020
Low glucose enhanced metformin's inhibitory effect on pancreatic cancer cells by suppressing glycolysis and inducing energy stress via up-regulation of miR-210-5p.
Article in Cell cycle (Georgetown, Tex.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.The Journal of biological chemistry · 2026Review
- Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis.Discover oncology · 2025Article
- Reprogramming of glucose metabolism in pancreatic cancer: mechanisms, implications, and therapeutic perspectives.Frontiers in immunology · 2025Review
- Metformin Inhibits the Progression of Pancreatic Cancer Through Regulating miR-378a-3p/VEGFA/RGC-32 Axis.Cancer medicine · 2024Article
- Non-coding RNAs as potential targets in metformin therapy for cancer.Cancer cell international · 2024Review
- Fasting and Glucose Metabolism Differentially Impact Peripheral Inflammation in Human Type 2 Diabetes.Nutrients · 2024Article
- Metformin and Glucose Concentration as Limiting Factors in Retinal Pigment Epithelial Cell Viability and Proliferation.International journal of molecular sciences · 2024Article
- Impact of Hypoxia-Induced miR-210 on Pancreatic Cancer.Current issues in molecular biology · 2023Review
- Pericyte-derived exosomal miR-210 improves mitochondrial function and inhibits lipid peroxidation in vascular endothelial cells after traumatic spinal cord injury by activating JAK1/STAT3 signaling pathway.Journal of nanobiotechnology · 2023Article
- MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications.Translational oncology · 2023Article
- Metformin enhances the antitumor activity of oncolytic herpes simplex virus HF10 (canerpaturev) in a pancreatic cell cancer subcutaneous model.Scientific reports · 2022Article
- The Impact of Epithelial-Mesenchymal Transition and Metformin on Pancreatic Cancer Chemoresistance: A Pathway towards Individualized Therapy.Medicina (Kaunas, Lithuania) · 2022Review
- Long noncoding RNA LINC00930 promotes PFKFB3-mediated tumor glycolysis and cell proliferation in nasopharyngeal carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions.International journal of molecular sciences · 2022Article
- Metabolic Control by DNA Tumor Virus-Encoded Proteins.Pathogens (Basel, Switzerland) · 2021Review
- How metformin affects various malignancies by means of microRNAs: a brief review.Cancer cell international · 2021Review
- Role of long intergenic non-protein coding RNA 00152 in pancreatic cancer glycolysisJournal of Cancer · 2021Article
- Quercetin Antagonizes Glucose Fluctuation Induced Renal Injury by Inhibiting Aerobic Glycolysis via HIF-1α/miR-210/ISCU/FeS Pathway.Frontiers in medicine · 2021Article
- Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development.Frontiers in oncology · 2021Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
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Abstract
To explore mechanisms underlying the discrepancy in anti-tumor effects of metformin on pancreatic cancer cells PANC-1 under different glucose conditions. We cultured PANC-1 cells in 25 mM and 5 mM glucose media, then treated with or without metformin. It showed that metformin significantly inhibited proliferation and viability, induced apoptosis of PANC-1 cells, which was more pronounced in low-glucose than in high-glucose group. Metformin up-regulated the expression of miR-210-5p in low glucose, but not in high glucose. miR-210-5p mimic inhibited the viability of PANC-1 cells and further enhanced the inhibitory effect of metformin. miR-210-5p down-regulated the expression of PFKFB2, a predicted target gene of miR-210-5p, reduced the activity of PFK1 and LDH. Metformin significantly inhibited the expression of phosphorylation-PFKFB2(p-PFKFB2) in the low-glucose group and inhibited the LDH activity both in the low and high glucose groups, thus inhibiting anaerobic glycolysis and inducing energy stress. Cells in the high glucose group could make a compensatory adaptation to the energy stress induced by metformin through increasing glucose consumption. However, due to the limited glucose supply and high dependence on anaerobic glycolysis of cells in the low glucose group, they couldn't make effective adaptive compensation. Therefore, cells in the low-glucose group were more vulnerable to the toxicity of metformin. In conclusion, the enhanced inhibitory effect of metformin on PANC-1 cells cultured in low glucose may be due to the up-regulation of the expression of miR-210-5p, then inhibiting anaerobic glycolytic flux and inducing energy stress via repressing the expression of p-PFKFB2 and activity of LDH. ABBREVIATIONS: PC: pancreatic cancer; DM: diabetes mellitus; PFKFB2: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase2; PFK1: phosphofructokinases; LDH: lactate dehydrogenase; F-2,6-BP: fructose 2,6-bisphosphate.
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