ArticleInternational journal of molecular sciences2017
The Effect of Metformin and GANT61 Combinations on the Radiosensitivity of Prostate Cancer Cells.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Metformin use and prostate cancer risk: A meta-analysis of cohort studies.Medicine · 2019 · on this mapPooled it
- Effects of silybin on triptorelin-induced bone metabolic abnormalities in prostate cancer revealed based on TMT-based proteomics.PloS one · 2026Article
- Metformin potentiates arsenic disulfide in diffuse large B-cell lymphoma: modulation of BAX/BCL-2 apoptotic pathway and hedgehog pathway.Frontiers in oncology · 2026Article
- Stemness regulation in prostate cancer: prostate cancer stem cells and targeted therapy.Annals of medicine · 2025Review
- Radiosensitizing Effects of Metformin on Ionizing Irradiation: An Overview of Animal and Clinical Studies.Current drug research reviews · 2025Review
- Prostate Cancer Stem Cells: Biology and Treatment Implications.International journal of molecular sciences · 2023Review
- Review
- Metformin Intervention-A Panacea for Cancer Treatment?Cancers · 2022Review
- Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models.Biomolecules · 2022Review
- Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area.International journal of molecular sciences · 2021Review
- Combined metformin-salicylate treatment provides improved anti-tumor activity and enhanced radiotherapy response in prostate cancer; drug synergy at clinically relevant doses.Translational oncology · 2021Article
- Pretreatment with metformin protects mice from whole-body irradiation.Journal of radiation research · 2021Article
- Fatty Acids Metabolism: The Bridge Between Ferroptosis and Ionizing Radiation.Frontiers in cell and developmental biology · 2021Review
- The Role of Hedgehog Pathway in Female Cancers.Journal of cancer science and clinical therapeutics · 2020Article
- Sonic Hedgehog/Gli1 Signaling Pathway Regulates Cell Migration and Invasion via Induction of Epithelial-to-mesenchymal Transition in Gastric Cancer.Journal of Cancer · 2020Article
- Combination Therapy With Charged Particles and Molecular Targeting: A Promising Avenue to Overcome Radioresistance.Frontiers in oncology · 2020Review
- The anticancer potential of metformin on prostate cancer.Prostate cancer and prostatic diseases · 2019Review
- Resveratrol Plays a Protective Role against Premature Ovarian Failure and Prompts Female Germline Stem Cell Survival.International journal of molecular sciences · 2019Article
- Hedgehog pathway inhibition causes primary follicle atresia and decreases female germline stem cell proliferation capacity or stemness.Stem cell research & therapy · 2019Article
- Heme Oxygenase-1 Inhibition Sensitizes Human Prostate Cancer Cells towards Glucose Deprivation and Metformin-Mediated Cell Death.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1). The effect on proliferation, radiosensitivity, apoptosis, cell cycle distribution, reactive oxygen species production, DNA repair, gene and protein expression was investigated. Furthermore, this treatment combination was also assessed in vivo. Metformin was shown to interact with Hh signaling by inhibiting the effector protein glioma-associated oncogene homolog 1 (GLI1) in PCa cells both in vitro and in vivo. The combination of metformin and GANT61 significantly inhibited PCa cell growth in vitro and enhanced the radiation response of 22Rv1 cells compared to either single agent. Nevertheless, neither the growth inhibitory effect nor the radiosensitization effect of the combination treatment observed in vitro was seen in vivo. Although the interaction between metformin and Hh signaling seems to be promising from a therapeutic point of view in vitro, more research is needed when implementing this combination strategy in vivo.
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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.