ArticleCell death & disease2014
Metformin promotes autophagy and apoptosis in esophageal squamous cell carcinoma by downregulating Stat3 signaling.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 3 of them syntheses that pooled it.
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Who cites it
172 citing papers in PubMed, 3 syntheses or guidelines pooled it, 268 citations in OpenAlex.
- The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021 · on this mapPooled it
- Effect of metformin on the mortality of colorectal cancer patients with T2DM: meta-analysis of sex differences.International journal of colorectal disease · 2020 · on this mapPooled it
- Tumor growth suppression by inhibiting both autophagy and STAT3 signaling in HNSCC.Oncotarget · 2015Pooled it
- Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA.Arthritis research & therapy · 2023Trial
- Genetic Variants inDiabetes · 2018Trial
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- p53 and p21 Status Influences Cellular Response to Metformin inCurrent issues in molecular biology · 2026Article
- Ceritinib induces ferroptosis via TRIM21-mediated GLUT1 ubiquitination and AMPK-driven metabolic reprogramming in breast cancer.iScience · 2026Article
- Metformin sensitizes esophageal squamous cell carcinoma to Vγ9Vδ2 T cell-mediated cytotoxicity by upregulating BTN3A1 and BTN2A1.Cell death & disease · 2026Article
- WDR72 Drives Esophageal Squamous Cell Carcinoma Progression by Inhibiting Autophagy via the PI3K/Akt/mTOR Pathway.The Kaohsiung journal of medical sciences · 2026Article
- Metformin in gastrointestinal cancers and inflammatory bowel disease: Unraveling its mechanisms and therapeutic applications.iScience · 2026Review
- Metformin Use and Development of Esophageal Squamous Cell Carcinoma.JAMA network open · 2026Article
- Venetoclax induces mitochondrial apoptosis and autophagy to overcome arsenic trioxide resistance in acute promyelocytic leukemia.Journal of translational medicine · 2026Article
- Diabetes Mellitus and the Prostate: The Odd Pairing.Cureus · 2025Review
- Investigation of the synergistic effect of metformin and FX11 on PANC-1 cell lines.Biological research · 2025Article
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Crosstalk between ferroptosis and autophagy: broaden horizons of cancer therapy.Journal of translational medicine · 2025Review
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antidiabetic drug metformin exerts chemopreventive and antineoplastic effects in many types of malignancies. However, the mechanisms responsible for metformin actions appear diverse and may differ in different types of cancer. Understanding the molecular and cellular mechanisms specific for different cancers is important to optimize strategy for metformin treatment in different cancer types. Here, we investigate the in vitro and in vivo effects of metformin on esophageal squamous cell carcinoma (ESCC) cells. Metformin selectively inhibited cell growth in ESCC tumor cells but not immortalized noncancerous esophageal epithelial cells. In addition to apoptosis, metformin triggered autophagy. Pharmacological or genetic inhibition of autophagy sensitized ESCC cells to metformin-induced apoptotic cell death. Mechanistically, signal transducer and activator of transcription 3 (Stat3) and its downstream target Bcl-2 was inactivated by metformin treatment. Accordingly, small interfering RNA (siRNA)-mediated Stat3 knockdown enhanced metformin-induced autophagy and apoptosis, and concomitantly enhanced the inhibitory effect of metformin on cell viability. Similarly, the Bcl-2 proto-oncogene, an inhibitor of both apoptosis and autophagy, was repressed by metformin. Ectopic expression of Bcl-2 protected cells from metformin-mediated autophagy and apoptosis. In vivo, metformin downregulated Stat3 activity and Bcl-2 expression, induced apoptosis and autophagy, and inhibited tumor growth. Together, inactivation of Stat3-Bcl-2 pathway contributes to metformin-induced growth inhibition of ESCC by facilitating crosstalk between apoptosis and autophagy.
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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.