ArticleCarcinogenesis2013
Metformin inhibits pancreatic cancer cell and tumor growth and downregulates Sp transcription factors.
Article in Carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Effect of Metformin and Statin Use on Survival in Pancreatic Cancer Patients: a Systematic Literature Review and Meta-analysis.Current medicinal chemistry · 2018Pooled it
- Evaluation of Mithramycin in Combination with Chemotherapeutic Agents Against Ewing Sarcoma Cell Lines.Cancers · 2025Article
- Obesity and Pancreatic Diseases: From Inflammation to Oncogenesis and the Impact of Weight Loss Interventions.Nutrients · 2025Review
- Methylstat sensitizes ovarian cancer cells to PARP-inhibition by targeting the histone demethylases JMJD1B/C.Cancer gene therapy · 2025Article
- Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Specificity Proteins (Sp) and Cancer.International journal of molecular sciences · 2023Review
- Metformin Induces Apoptosis in Human Pancreatic Cancer (PC) Cells Accompanied by Changes in the Levels of Histone Acetyltransferases (Particularly, p300/CBP-Associated Factor (PCAF) Protein Levels).Pharmaceuticals (Basel, Switzerland) · 2023Article
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Promise of metformin for preventing age-related cognitive dysfunction.Neural regeneration research · 2022Review
- Development of an Icariin-Loaded Bilosome-Melittin Formulation with Improved Anticancer Activity against Cancerous Pancreatic Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Specificity protein 1-activated bone marrow stromal cell antigen 2 accelerates pancreatic cancer cell proliferation and migration.Experimental and therapeutic medicine · 2021Article
- Repurposing metformin for the treatment of gastrointestinal cancer.World journal of gastroenterology · 2021Review
- Anticancer potential of metformin: focusing on gastrointestinal cancers.Cancer chemotherapy and pharmacology · 2021Review
- Article
- Repurposing metformin, simvastatin and digoxin as a combination for targeted therapy for pancreatic ductal adenocarcinoma.Cancer letters · 2020Article
- Cohort Study of Antihyperglycemic Medication and Pancreatic Cancer Patients Survival.International journal of environmental research and public health · 2020Article
- Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-β-hydroxymaytenin Obtained from CultivatedMolecules (Basel, Switzerland) · 2020Article
- Ursolic acid promotes apoptosis and mediates transcriptional suppression of CT45A2 gene expression in non-small-cell lung carcinoma harbouring EGFR T790M mutations.British journal of pharmacology · 2019Article
- Anti-cancer activity of the novel 2-hydroxydiarylamide derivatives IMD-0354 and KRT1853 through suppression of cancer cell invasion, proliferation, and survival mediated by TMPRSS4.Scientific reports · 2019Article
- Role of p53 Family Proteins in Metformin Anti-Cancer Activities.Journal of Cancer · 2019Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Metformin is a widely used antidiabetic drug, and epidemiology studies for pancreatic and other cancers indicate that metformin exhibits both chemopreventive and chemotherapeutic activities. Several metformin-induced responses and genes are similar to those observed after knockdown of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 by RNA interference, and we hypothesized that the mechanism of action of metformin in pancreatic cancer cells was due, in part, to downregulation of Sp transcription factors. Treatment of Panc1, L3.6pL and Panc28 pancreatic cancer cells with metformin downregulated Sp1, Sp3 and Sp4 proteins and several pro-oncogenic Sp-regulated genes including bcl-2, survivin, cyclin D1, vascular endothelial growth factor and its receptor, and fatty acid synthase. Metformin induced proteasome-dependent degradation of Sps in L3.6pL and Panc28 cells, whereas in Panc1 cells metformin decreased microRNA-27a and induced the Sp repressor, ZBTB10, and disruption of miR-27a:ZBTB10 by metformin was phosphatase dependent. Metformin also inhibited pancreatic tumor growth and downregulated Sp1, Sp3 and Sp4 in tumors in an orthotopic model where L3.6pL cells were injected directly into the pancreas. The results demonstrate for the first time that the anticancer activities of metformin are also due, in part, to downregulation of Sp transcription factors and Sp-regulated genes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.