ArticleCancer research2009
Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02978547 (The Effects of Neoadjuvant Metformin on Tumour Cell Proliferation and Tumour Progression in Pancreatic Ductal Adenocarcinoma), which is not on this map. Cited by 172 papers, 4 of them syntheses that pooled it.
What it found
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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.
The Effects of Neoadjuvant Metformin on Tumour Cell Proliferation and Tumour Progression in Pancreatic Ductal Adenocarcinoma
Who cites it
172 citing papers in PubMed, 4 syntheses or guidelines pooled it, 315 citations in OpenAlex.
- The addition of metformin to systemic anticancer therapy in advanced or metastatic cancers: a meta-analysis of randomized controlled trials.International journal of medical sciences · 2020Pooled it
- Effect of Metformin and Statin Use on Survival in Pancreatic Cancer Patients: a Systematic Literature Review and Meta-analysis.Current medicinal chemistry · 2018Pooled it
- Impact of diabetes mellitus on clinical outcomes of pancreatic cancer after surgical resection: A systematic review and meta-analysis.PloS one · 2017Pooled it
- Effect of Metformin Use on Survival in Resectable Pancreatic Cancer: A Single-Institution Experience and Review of the Literature.PloS one · 2016Pooled it
- Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.JNCI cancer spectrum · 2023 · on this mapTrial
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- The prognostic value of calcium channel blockers usage for overall survival and recurrence-free survival in patients with endometrial cancer.European journal of medical research · 2025Article
- Investigation of the synergistic effect of metformin and FX11 on PANC-1 cell lines.Biological research · 2025Article
- Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status.Signal transduction and targeted therapy · 2025Review
- Review
- The role of AMPK in pancreatic cancer: from carcinogenesis to treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Caffeine Inhibits Both Basal and Insulin-Activated Urate Transport.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Cuproptosis-related lncRNAs are correlated with tumour metabolism and immune microenvironment and predict prognosis in pancreatic cancer patients.IET systems biology · 2023Article
- Statins inhibit protein kinase D (PKD) activation in intestinal cells and prevent PKD1-induced growth of murine enteroids.American journal of physiology. Cell physiology · 2023Article
- Review
- Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study.Molecular biomedicine · 2022Review
- Opposite Effects of Src Family Kinases on YAP and ERK Activation in Pancreatic Cancer Cells: Implications for Targeted Therapy.Molecular cancer therapeutics · 2022Article
- Metformin Use May Increase Risk of Pancreatic Cancer in Diabetic Women: An Analysis of the Korean National Health Insurance Service-National Health Screening Cohort Database.Korean journal of family medicine · 2022Article
- Review
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells. Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway. Metformin, the most widely used drug in the treatment of type 2 diabetes, activates AMP kinase (AMPK), which negatively regulates mTOR. Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells. Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II). Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone. Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions. Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists. Treatment with metformin induced striking and sustained increase in the phosphorylation of AMPK at Thr(172) and a selective AMPK inhibitor (compound C, at 5 micromol/L) reversed the effects of metformin on [Ca(2+)](i) and DNA synthesis, indicating that metformin acts through AMPK activation. In view of these results, we tested whether metformin inhibits pancreatic cancer growth. Administration of metformin significantly decreased the growth of MIAPaCa-2 and PANC-1 cells xenografted on the flank of nude mice. These results raise the possibility that metformin could be a potential candidate in novel treatment strategies for human pancreatic cancer.
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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.