ArticleGynecologic oncology2012
Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway.
Article in Gynecologic oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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The trial behind it
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Who cites it
65 citing papers in PubMed, 146 citations in OpenAlex.
- A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: An NRG oncology/GOG study.Gynecologic oncology · 2025Trial
- Conservative therapy with metformin plus megestrol acetate for endometrial atypical hyperplasia.Journal of gynecologic oncology · 2014Trial
- Effects of Metformin Treatment Against Endometrial Cancer Cells Cultured In Vitro or Grafted into Female Balb/C Nude Mice: Insights into Cell Response and IGF-1R and PI3K/AKT/mTOR Signaling Pathways.Cell biochemistry and biophysics · 2025Article
- Development of 3D Cell-Based Fluorescent Reporter Assay for Screening of Drugs Downregulating Telomerase Reverse Transcriptase.Bioengineering (Basel, Switzerland) · 2025Article
- A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer.Gynecologic oncology · 2025Article
- Recent therapeutic advances in gynecologic oncology: evolving roles of immunotherapy, antibody-drug conjugates, and clinical trial innovations.Frontiers in oncology · 2025Review
- Pyrazoline B Induces Oxidative Stress Mediated Toxicity, Cell Cycle Arrest, and Caspase-Independent Apoptosis in BT-474 Human Breast Cancer Cells.Journal of experimental pharmacology · 2025Article
- Metformin in gynecological disorders: pathogenic insights and therapeutic implications.Frontiers in pharmacology · 2025Review
- Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-oncology Research.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Small molecule targeted therapies for endometrial cancer: progress, challenges, and opportunities.RSC medicinal chemistry · 2024Review
- Regulation of Protein-Induced Apoptosis and Autophagy in Human Hepatocytes Treated with Metformin and Paclitaxel In Silico and In Vitro.Biomedicines · 2023Article
- The development and benefits of metformin in various diseases.Frontiers of medicine · 2023Review
- Metformin - its anti-cancer effects in hematologic malignancies.Oncology reviews · 2021Article
- Metformin regulation of progesterone receptor isoform-B expression in human endometrial cancer cells is glucose-dependent.Oncology letters · 2020Article
- Recycling the Purpose of Old Drugs to Treat Ovarian Cancer.International journal of molecular sciences · 2020Review
- Route-specific association of progestin therapy and concurrent metformin use in obese women with complex atypical hyperplasia.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2020Article
- Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.Marine drugs · 2020Article
- Associations between metabolic syndrome and gynecologic cancer.Obstetrics & gynecology science · 2020Review
- Novel Metformin-Based Schiff Bases: Synthesis, Characterization, and Antibacterial Evaluation.Materials (Basel, Switzerland) · 2020Article
- Buformin suppresses osteosarcoma via targeting AMPK signaling pathway.Open life sciences · 2020Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesTo examine the effects of combination therapy with metformin and paclitaxel in endometrial cancer cell lines.
methodsECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed after exposure to paclitaxel and metformin. Cell cycle progression was assessed by flow cytometry. hTERT expression was determined by real-time RT-PCR. Western immunoblotting was performed to determine the effect of metformin/paclitaxel on the mTOR pathway.
resultsPaclitaxel inhibited proliferation in a dose-dependent manner in both cell lines with IC(50) values of 1-5nM and 5-10nM for Ishikawa and ECC-1 cells, respectively. Simultaneous exposure of cells to various doses of paclitaxel in combination with metformin (0.5mM) resulted in a significant synergistic anti-proliferative effect in both cell lines (Combination Index<1). Metformin induced G1 arrest in both cell lines. Paclitaxel alone or in combination with metformin resulted in predominantly G2 arrest. Metformin decreased hTERT mRNA expression while paclitaxel alone had no effect on telomerase activity. Metformin stimulated AMPK phosphorylation and decreased phosphorylation of the S6 protein. In contrast, paclitaxel inhibited AMPK phosphorylation in the ECC-1 cell line and induced phosphorylation of S6 in both cell lines. Treatment with metformin and paclitaxel resulted in decreased phosphorylation of S6 in both cell lines but only had an additive effect on AMPK phosphorylation in the ECC-1 cell line.
conclusionsMetformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway. This combination may be a promising targeted therapy for endometrial cancer.
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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.