ArticleOncotarget2016
Metformin mediates resensitivity to 5-fluorouracil in hepatocellular carcinoma via the suppression of YAP.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Metformin effects on head and neck squamous carcinoma microenvironment: Window of opportunity trial.The Laryngoscope · 2017Trial
- Mapping the current research landscape of metformin in cancer based on bibliometric analysis.Discover oncology · 2025Article
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- Targeting the Hippo/YAP1 signaling pathway in hepatocellular carcinoma: From mechanisms to therapeutic drugs (Review).International journal of oncology · 2024Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Antitumor Activity of Metformin Combined with Locoregional Therapy for Liver Cancer: Evidence and Future Directions.Cancers · 2023Review
- Article
- Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression.Bone research · 2023Article
- The development and benefits of metformin in various diseases.Frontiers of medicine · 2023Review
- Studying the Geroprotective Properties of YAP/TAZ Signaling Inhibitors onInternational journal of molecular sciences · 2023Article
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- Hippo Signaling in the Ovary: Emerging Roles in Development, Fertility, and Disease.Endocrine reviews · 2022Review
- Targeting the Hippo Pathway in Gastric Cancer and Other Malignancies in the Digestive System: From Bench to Bedside.Biomedicines · 2022Review
- Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Metformin Enhancement of Therapeutic Effects of 5-Fluorouracil and Oxaliplatin in Colon Cancer Cells and Nude Mice.Biomedicines · 2022Article
- Role of metformin in the diagnosis, prevention, and treatment of hepatocellular carcinoma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Metformin: review of epidemiology and mechanisms of action in pancreatic cancer.Cancer metastasis reviews · 2021Review
- Downregulation of MicroRNA-130a Inhibits Oral Squamous Cell Carcinoma Proliferation and Metastasis via the Hippo-YAP Pathway.Cancer management and research · 2021Article
- Recent Advances of the Hippo/YAP Signaling Pathway in Brain Development and Glioma.Cellular and molecular neurobiology · 2020Review
- Yes-Associated Protein Contributes to Cell Proliferation and Migration of Gastric Cancer via Activation of Gli1.OncoTargets and therapy · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin plays an anti-proliferative role in tumor cells in many types of cancer. However, the correlation between metformin and sensitivity to chemotherapeutic agents in hepatocellular carcinoma (HCC) and the relevant mechanism are unclear. The present study showed that HCC patients with type 2 diabetes mellitus benefited from metformin administration, with a longer overall survival. Metformin resensitized Bel-7402/5-fluorouracil (Bel/Fu) cells to 5-fluorouracil (5-Fu) in vitro and in vivo, and the combination of metformin and 5-Fu inhibited cell proliferation, promoted cell apoptosis and induced G0/G1 cell cycle arrest in the Bel/Fu cells. Moreover, metformin repressed YAP by both decreasing the total protein expression and accelerating the phosphorylation of YAP. The inhibition of YAP subsequently promoted the expression of PTEN, and suppressed the Akt pathway. Therefore, the expression of P-gp and MRP1 was downregulated. Taken together, our findings suggested that metformin may increase sensitivity to chemotherapeutic agents by suppressing YAP in hepatocellular carcinoma.
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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.