ArticleOncotarget2015
Metformin and temozolomide act synergistically to inhibit growth of glioma cells and glioma stem cells in vitro and in vivo.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
- Harnessing Repurposed Drugs to Enhance Temozolomide Efficacy in Glioblastoma.Cancer reports (Hoboken, N.J.) · 2026Review
- Metformin Suppresses Glioblastoma Tumor Growth and Progression Through the AMPK/FoxO3a/Survivin Axis.Cells · 2026Article
- Atypical cadherin FAT1 promotes tumorigenesis by suppressing autophagic cell death in glioblastoma under hypoxia or nutrient stress.Cellular & molecular biology letters · 2025Article
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin.Frontiers in oncology · 2025Review
- Drug Repurposing: A Conduit to Unravelling Metabolic Reprogramming for Cancer Treatment.Mini reviews in medicinal chemistry · 2025Review
- Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments.World journal of stem cells · 2024Article
- Advances in Anti-Cancer Drug Development: Metformin as Anti-Angiogenic Supplemental Treatment for Glioblastoma.International journal of molecular sciences · 2024Review
- Could Metformin and Resveratrol Support Glioblastoma Treatment? A Mechanistic View at the Cellular Level.Cancers · 2023Review
- Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study).Discover oncology · 2023Article
- Glioblastoma Metabolism: Insights and Therapeutic Strategies.International journal of molecular sciences · 2023Review
- Ion Channels in Gliomas-From Molecular Basis to Treatment.International journal of molecular sciences · 2023Review
- The dark side of mRNA translation and the translation machinery in glioblastoma.Frontiers in cell and developmental biology · 2023Review
- GDNF regulates lipid metabolism and glioma growth through RET/ERK/HIF‑1/SREBP‑1.International journal of oncology · 2022Article
- Mechanical Properties of the Extracellular Environment of Human Brain Cells Drive the Effectiveness of Drugs in Fighting Central Nervous System Cancers.Brain sciences · 2022Review
- Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma.International journal of molecular sciences · 2022Review
- ERK inhibition in glioblastoma is associated with autophagy activation and tumorigenesis suppression.Journal of neuro-oncology · 2022Article
- Review
- Metabolic adaptations in cancers expressing isocitrate dehydrogenase mutations.Cell reports. Medicine · 2021Review
- Pharmacological strategies for improving the prognosis of glioblastoma.Expert opinion on pharmacotherapy · 2021Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In spite of advances in diagnosis and therapy, the prognosis of patients with GBM has remained dismal. The fast recurrence and multi-drug resistance are some of the key challenges in combating brain tumors. Glioma stem cells (GSCs) which are considered the source of relapse and chemoresistance, the need for more effective therapeutic options is overwhelming. In our present work, we found that combined treatment with temozolomide (TMZ) and metformin (MET) synergistically inhibited proliferation and induced apoptosis in both glioma cells and GSCs. Combination of TMZ and MET significantly reduced the secondary gliosphere formation and expansion of GSCs. We first demonstrated that MET effectively inhibited the AKT activation induced by TMZ, and a combination of both drugs led to enhanced reduction of mTOR, 4EBP1 and S6K phosphorylation. In addition, the combination of the two drugs was accompanied with a powerful AMP-activated protein kinase (AMPK) activation, while this pathway is not determinant. Xenografts performed in nude mice demonstrate in vivo demonstrated that combined treatment significantly reduced tumor growth rates and prolonged median survival of tumor-bearing mice. In conclusion, TMZ in combination with MET synergistically inhibits the GSCs proliferation through downregulation of AKT-mTOR signaling pathway. The combined treatment of two drugs inhibits GSCs self-renewal capability and partly eliminates GSCs in vitro and in vivo. This combined treatment could be a promising option for patients with advanced GBM.
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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.