ArticleBritish journal of cancer2020
Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- PSPH Promotes Hepatocellular Carcinoma Progression by Upregulating HIF-1α and Is Regulated by LncRNA GSEC/miR-101-3p.Current issues in molecular biology · 2026Article
- High glucose levels promote glycolysis and cholesterol synthesis via ERRα and suppress the autophagy-lysosomal pathway in endometrial cancer.Cell death & disease · 2025Article
- Combined Oxygen-Enhanced MRI and Perfusion Imaging Detect Hypoxia Modification from Banoxantrone and Atovaquone and Track Their Differential Mechanisms of Action.Cancer research communications · 2024Article
- Hypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies.Redox biology · 2024Review
- Glucose metabolism reprogramming in gynecologic malignant tumors.Journal of Cancer · 2024Review
- Anti-VEGF therapy selects for clones resistant to glucose starvation in ovarian cancer xenografts.Journal of experimental & clinical cancer research : CR · 2023Article
- Platycodin D inhibits the proliferation, invasion and migration of endometrial cancer cells by blocking the PI3K/Akt signaling pathway via ADRA2A upregulation.Oncology letters · 2023Article
- Metformin Impacts Human Syncytiotrophoblast Mitochondrial Function from Pregnancies Complicated by Obesity and Gestational Diabetes Mellitus in a Sexually Dimorphic Manner.Antioxidants (Basel, Switzerland) · 2023Article
- Glucose metabolic reprogramming and its therapeutic potential in obesity-associated endometrial cancer.Journal of translational medicine · 2023Review
- Metformin is a metabolic modulator and radiosensitiser in rectal cancer.Frontiers in oncology · 2023Article
- Magnetic resonance spectroscopy associations with clinicopathologic features of estrogen-dependent endometrial cancer.BMC medical imaging · 2022Article
- Endometrial Cancer Stem Cells: Where Do We Stand and Where Should We Go?International journal of molecular sciences · 2022Review
- Targeting Cancer Metabolism Plasticity with JX06 Nanoparticles via Inhibiting PDK1 Combined with Metformin for Endometrial Cancer Patients with Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Long non-coding RNA PAARH promotes hepatocellular carcinoma progression and angiogenesis via upregulating HOTTIP and activating HIF-1α/VEGF signaling.Cell death & disease · 2022Article
- Rewired Cellular Metabolic Profiles in Response to Metformin under Different Oxygen and Nutrient Conditions.International journal of molecular sciences · 2022Article
- Identification and Validation of Cuproptosis-Related Prognostic Signature and Associated Regulatory Axis in Uterine Corpus Endometrial Carcinoma.Frontiers in genetics · 2022Article
- Article
- The updated landscape of tumor microenvironment and drug repurposing.Signal transduction and targeted therapy · 2020Review
- Development of cancer metabolism as a therapeutic target: new pathways, patient studies, stratification and combination therapy.British journal of cancer · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHigh expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin's anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin.
methodsEndometrial cancer biopsies from women treated with pre-surgical metformin were tested for the hypoxia markers, HIF-1α and CA-9. Endometrial cancer cell lines were treated with metformin in variable glucose concentrations in normoxia or hypoxia and cell viability, mitochondrial biogenesis, function and energy metabolism were assessed.
resultsIn women treated with metformin (n = 28), Ki-67 response was lower in hypoxic tumours. Metformin showed minimal cytostatic effects towards Ishikawa and HEC1A cells in conventional medium (25 mM glucose). In low glucose (5.5 mM), a dose-dependent cytostatic effect was observed in normoxia but attenuated in hypoxia. Tumours treated with metformin showed increased mitochondrial mass (n = 25), while in cultured cells metformin decreased mitochondrial function. Metformin targets mitochondrial respiration, however, in hypoxic, high glucose conditions, there was a switch to glycolytic metabolism and decreased metformin response.
conclusionsUnderstanding the metabolic adaptations of endometrial tumours may identify patients likely to derive clinical benefit from metformin.
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