ArticlePloS one2015
Metformin Causes G1-Phase Arrest via Down-Regulation of MiR-221 and Enhances TRAIL Sensitivity through DR5 Up-Regulation in Pancreatic Cancer Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Gastric bypass surgery with exercise alters plasma microRNAs that predict improvements in cardiometabolic risk.International journal of obesity (2005) · 2017Trial
- 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
- Molecular Landscape of Pelvic Organ Prolapse Provides Insights into Disease Etiology.International journal of molecular sciences · 2023Article
- 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
- miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.Molecular therapy. Nucleic acids · 2022Review
- Metformin attenuates V-domain Ig suppressor of T-cell activation through the aryl hydrocarbon receptor pathway in Melanoma: In Vivo and In Vitro Studies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Drug Repurposing, an Attractive Strategy in Pancreatic Cancer Treatment: Preclinical and Clinical Updates.Cancers · 2021Review
- Upregulation of endogenous TRAIL-elicited apoptosis is essential for metformin-mediated antitumor activity against TNBC and NSCLC.Molecular therapy oncolytics · 2021Article
- How metformin affects various malignancies by means of microRNAs: a brief review.Cancer cell international · 2021Review
- Anesthetics may modulate cancer surgical outcome: a possible role of miRNAs regulation.BMC anesthesiology · 2021Review
- Cohort Study of Antihyperglycemic Medication and Pancreatic Cancer Patients Survival.International journal of environmental research and public health · 2020Article
- MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients.Non-coding RNA · 2020Review
- Metformin Treatment Suppresses Melanoma Cell Growth and Motility Through Modulation of microRNA Expression.Cancers · 2019Article
- SUN2: A potential therapeutic target in cancer.Oncology letters · 2019Review
- lncRNA GAS5 Reverses EMT and Tumor Stem Cell-Mediated Gemcitabine Resistance and Metastasis by Targeting miR-221/SOCS3 in Pancreatic Cancer.Molecular therapy. Nucleic acids · 2018Article
- Review
- Metformin sensitizes triple-negative breast cancer to proapoptotic TRAIL receptor agonists by suppressing XIAP expression.Breast cancer research and treatment · 2017Article
- Ellagic acid inhibits the proliferation of human pancreatic carcinoma PANC-1 cells in vitro and in vivo.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although many chemotherapeutic strategies against cancer have been developed, pancreatic cancer is one of the most aggressive and intractable types of malignancies. Therefore, new strategies and anti-cancer agents are necessary to treat this disease. Metformin is a widely used drug for type-2 diabetes, and is also known as a promising candidate anti-cancer agent from recent studies in vitro and in vivo. However, the mechanisms of metformin's anti-cancer effects have not been elucidated. We demonstrated that metformin suppressed the expression of miR-221, one of the most well-known oncogenic microRNAs, in human pancreatic cancer PANC-1 cells. Moreover, we showed that the down-regulation of miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of the direct targets of miR-221. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is also a promising agent for cancer treatment. While recent studies showed that treatment with only TRAIL was not effective against pancreatic cancer cells, the present data showed that metformin sensitized p53-mutated pancreatic cancer cells to TRAIL. Metformin induced the expressions of death receptor 5 (DR5), a receptor for TRAIL, and Bim with a pro-apoptotic function in the downstream of TRAIL-DR5 pathway. We suggest that the up-regulation of these proteins may contribute to sensitization of TRAIL-induced apoptosis. The combination therapy of metformin and TRAIL could therefore be effective in the treatment of pancreatic cancer.
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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.