ArticleBreast cancer research : BCR2019
Metformin overcomes resistance to cisplatin in triple-negative breast cancer (TNBC) cells by targeting RAD51.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 139 citations in OpenAlex.
- Ellagic Acid and Metformin: In Vitro Synergy and Enhanced Cisplatin Efficacy In Vivo in Resistant Breast Cancer.Nutrients · 2026Article
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Metformin drives HIF-1α-mediated dual metabolic reprogramming to enhance γδ T cell therapy in triple-negative breast cancer.Cancer immunology, immunotherapy : CII · 2026Article
- The Mevalonate Pathway in the Radiation Response of Cancer.International journal of radiation oncology, biology, physics · 2025Review
- Article
- Metformin-Based Combination Approaches for Triple-Negative Breast Cancer.Pharmaceutics · 2025Review
- Metformin sensitizes triple-negative breast cancer to histone deacetylase inhibitors by targeting FGFR4.Journal of biomedical science · 2025Article
- Omega-3 fatty acids: molecular weapons against chemoresistance in breast cancer.Cellular & molecular biology letters · 2025Review
- Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.Pharmaceutical research · 2025Review
- Metformin Enhances the Chemosensitivity of Gastric Cancer to Cisplatin by Downregulating Nrf2 Level.Analytical cellular pathology (Amsterdam) · 2025Article
- Metformin Inhibited GSDME to Suppress M2 Macrophage Pyroptosis and Maintain M2 Phenotype to Mitigate Cisplatin-Induced Intestinal Inflammation.Biomedicines · 2024Article
- Deubiquitinating enzyme USP28 inhibitor AZ1 alone and in combination with cisplatin for the treatment of non-small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2024Article
- CircCDYL2 bolsters radiotherapy resistance in nasopharyngeal carcinoma by promoting RAD51 translation initiation for enhanced homologous recombination repair.Journal of experimental & clinical cancer research : CR · 2024Article
- Bisbiguanide analogs induce mitochondrial stress to inhibit lung cancer cell invasion.iScience · 2024Article
- Drug Resistance and Novel Targets for Cancer Therapy: An Overview of Recent Findings.Biomedicines · 2024Article
- Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Lactylation-related gene signature for prognostic prediction and immune infiltration analysis in breast cancer.Heliyon · 2024Article
- Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Article
- p32/OPA1 axis-mediated mitochondrial dynamics contributes to cisplatin resistance in non-small cell lung cancer.Acta biochimica et biophysica Sinica · 2024Article
- Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemotherapy is a standard therapeutic regimen to treat triple-negative breast cancer (TNBC); however, chemotherapy alone does not result in significant improvement and often leads to drug resistance in patients. In contrast, combination therapy has proven to be an effective strategy for TNBC treatment. Whether metformin enhances the anticancer effects of cisplatin and prevents cisplatin resistance in TNBC cells has not been reported.
methodsCell viability, wounding healing, and invasion assays were performed on Hs 578T and MDA-MB-231 human TNBC cell lines to demonstrate the anticancer effects of combined cisplatin and metformin treatment compared to treatment with cisplatin alone. Western blotting and immunofluorescence were used to determine the expression of RAD51 and gamma-H2AX. In an in vivo 4T1 murine breast cancer model, a synergistic anticancer effect of metformin and cisplatin was observed.
resultsCisplatin combined with metformin decreased cell viability and metastatic effect more than cisplatin alone. Metformin suppressed cisplatin-mediated RAD51 upregulation by decreasing RAD51 protein stability and increasing its ubiquitination. In contrast, cisplatin increased RAD51 expression in an ERK-dependent manner. In addition, metformin also increased cisplatin-induced phosphorylation of γ-H2AX. Overexpression of RAD51 blocked the metformin-induced inhibition of cell migration and invasion, while RAD51 knockdown enhanced cisplatin activity. Moreover, the combination of metformin and cisplatin exhibited a synergistic anticancer effect in an orthotopic murine model of 4T1 breast cancer in vivo.
conclusionsMetformin enhances anticancer effect of cisplatin by downregulating RAD51 expression, which represents a novel therapeutic target in TNBC management.
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