ArticleInternational journal of molecular sciences2021
Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- PARP inhibitors target cellular energy metabolism: Mechanisms of action and clinical implications.Translational oncology · 2026Review
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- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Metformin suppressed epithelial-mesenchymal transition, cisplatin resistance and metastatic potential of ovarian cancer via inhibiting TGF-β1/Smads.Translational cancer research · 2026Article
- Metformin-A Type 2 Diabetes Mellitus Drug-And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Impairment of oxidative metabolism compromises Rad51 recruitment and potentiates PARP inhibitor effectiveness in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Enhancing PARP inhibitor efficacy in ovarian cancer: targeting the PI3K/AKT/mTOR pathway.Journal of ovarian research · 2025Review
- Mechanisms of Resistance to PARPi in Pancreatic Ductal Adenocarcinoma.Journal of cellular and molecular medicine · 2025Article
- Article
- O-GlcNAcylation in ovarian tumorigenesis and its therapeutic implications.Translational oncology · 2025Review
- Claudin-4 remodeling of nucleus-cell cycle crosstalk maintains ovarian tumor genome stability and drives resistance to genomic instability-inducing agents.bioRxiv : the preprint server for biology · 2024Article
- Bidirectional pharmacokinetic drug interactions between olaparib and metformin.Cancer chemotherapy and pharmacology · 2024Article
- Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Auranofin Synergizes with the PARP Inhibitor Olaparib to Induce ROS-Mediated Cell Death in Mutant p53 Cancers.Antioxidants (Basel, Switzerland) · 2023Article
- Determination of Apoptotic Mechanism of Action of Tetrabromobisphenol A and Tetrabromobisphenol S in Human Peripheral Blood Mononuclear Cells: A Comparative Study.Molecules (Basel, Switzerland) · 2022Article
- Review
- Synergic Effect of Metformin and Everolimus on Mitochondrial Dynamics of Renal Cell Carcinoma.Genes · 2022Article
- Metformin: A promising drug for human cancers.Oncology letters · 2022Review
- Article
- Advances in Gynecological Cancers.International journal of molecular sciences · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
This study examined the effect of combination treatment with the poly (ADP-ribose) polymerase inhibitor olaparib and metformin on homologous recombination (HR)-proficient epithelial ovarian cancer (EOC). Ovarian cancer cell lines (OV-90 and SKOV-3) were treated with olaparib, metformin, or a combination of both. Cell viability was assessed by MTT and colony formation assays. The production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential were examined using the specific fluorescence probes, DCFH2-DA (2',7'-dichloro-dihydrofluorescein diacetate) and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine). Apoptotic and necrotic changes were measured by double staining with Hoechst 33258 and propidium iodide, orange acridine and ethidium bromide staining, phosphatidylserine externalization, TUNEL assay, caspase 3/7 activity, and cytochrome c and p53 expression. Compared with single-drug treatment, the combination of olaparib and metformin significantly inhibited cell proliferation and colony formation in HR-proficient ovarian cancer cells. ROS production preceded a decrease in mitochondrial membrane potential. The changes in ROS levels suggested their involvement in inducing apoptosis in response to combination treatment. The present results indicate a shift towards synergism in cells with mutant or null p53, treated with olaparib combined with metformin, providing a new approach to the treatment of gynecologic cancers. Taken together, the results support the use of metformin to sensitize EOC to olaparib therapy.
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