ArticleOncotarget2016
Metformin represses bladder cancer progression by inhibiting stem cell repopulation via COX2/PGE2/STAT3 axis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Metformin as an anti-cancer agent against bladder cancer acts via PD-L1 downregulation in an orthotopic mouse model.BMC cancer · 2025Article
- Recent advances in bladder cancer stem cells (BCSCs): A descriptive review of emerging therapeutic targets.iScience · 2025Review
- Harnessing Oxylipins and Inflammation Modulation for Prevention and Treatment of Colorectal Cancer.International journal of molecular sciences · 2024Review
- Strategies for Overcoming Immune Evasion in Bladder Cancer.International journal of molecular sciences · 2024Review
- Targeted therapies in bladder cancer: signaling pathways, applications, and challenges.MedComm · 2023Review
- The Bladder Tumor Microenvironment Components That Modulate the Tumor and Impact Therapy.International journal of molecular sciences · 2023Review
- Article
- Overview of Prostaglandin E2 (PGE2)-Targeting Radiolabelled Imaging Probes from Preclinical Perspective: Lessons Learned and Road Ahead.International journal of molecular sciences · 2023Review
- Apoptosis as Driver of Therapy-Induced Cancer Repopulation and Acquired Cell-Resistance (CRAC): A Simple In Vitro Model of Phoenix Rising in Prostate Cancer.International journal of molecular sciences · 2022Article
- Cyclooxygenase-2 expression is associated with chemoresistance through cancer stemness property in hypopharyngeal carcinoma.Oncology letters · 2021Article
- Lifestyle and Non-muscle Invasive Bladder Cancer Recurrence, Progression, and Mortality: Available Research and Future Directions.Bladder cancer (Amsterdam, Netherlands) · 2020Article
- Metformin Combined with 4SC-202 Inhibited the Migration and Invasion of OSCC via STAT3/TWIST1.OncoTargets and therapy · 2020Article
- Study protocol of a phase II clinical trial of oral metformin for the intravesical treatment of non-muscle invasive bladder cancer.BMC cancer · 2019Article
- Metformin targets a YAP1-TEAD4 complex via AMPKα to regulate CCNE1/2 in bladder cancer cells.Journal of experimental & clinical cancer research : CR · 2019Article
- The Biguanides Metformin and Buformin in Combination with 2-Deoxy-glucose or WZB-117 Inhibit the Viability of Highly Resistant Human Lung Cancer Cells.Stem cells international · 2019Article
- Pre-clinical effects of metformin and aspirin on the cell lines of different breast cancer subtypes.Investigational new drugs · 2018Article
- Pleiotropic Effects of Metformin on Cancer.International journal of molecular sciences · 2018Review
- A novel BRCA2 mutation in prostate cancer sensitive to combined radiotherapy and androgen deprivation therapy.Cancer biology & therapy · 2018Article
- Effects of metformin on the expression of AMPK and STAT3 in the spinal dorsal horn of rats with neuropathic pain.Molecular medicine reports · 2018Article
- Metformin exerts multitarget antileukemia activity in JAK2Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) are a sub-population of tumor cells playing essential roles in initiation, differentiation, recurrence, metastasis and development of drug resistance of various cancers, including bladder cancer. Although multiple lines of evidence suggest that metformin is capable of repressing CSC repopulation in different cancers, the effect of metformin on bladder cancer CSCs remains largely unknown. Using the N-methyl-N-nitrosourea (MNU)-induced rat orthotropic bladder cancer model, we demonstrated that metformin is capable of repressing bladder cancer progression from both mild to moderate/severe dysplasia lesions and from carcinoma in situ (CIS) to invasive lesions. Metformin also can arrest bladder cancer cells in G1/S phases, which subsequently leads to apoptosis. And also metformin represses bladder cancer CSC repopulation evidenced by reducing cytokeratin 14 (CK14+) and octamer-binding transcription factor 3/4 (OCT3/4+) cells in both animal and cellular models. More importantly, we found that metformin exerts these anticancer effects by inhibiting COX2, subsequently PGE2 as well as the activation of STAT3. In conclusion, we are the first to systemically demonstrate in both animal and cell models that metformin inhibits bladder cancer progression by inhibiting stem cell repopulation through the COX2/PGE2/STAT3 axis.
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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.