ArticleFrontiers in oncology2019
Role of Metformin and AKT Axis Modulation in the Reversion of Hypoxia Induced TMZ-Resistance in Glioma Cells.
Article in Frontiers in oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- miRNA675-5p inhibitor's dual role as novel therapeutic alternative or sensitizing treatment in resistant glioma models.Molecular therapy. Nucleic acids · 2026Article
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.International journal of molecular sciences · 2026Review
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Radio-chemotherapy and metformin selectively modulate the heterogeneous landscape of glioma with ribosome biogenesis, long non coding RNA and immune-escape markers as major player.International journal of biological sciences · 2025Article
- Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin.Frontiers in oncology · 2025Review
- Fast detection of protein kinase B in chrysin treated colorectal cancer cells using a novel multicore microfiber biosensor.Communications engineering · 2024Article
- Preclinical and clinical advances to overcome hypoxia in glioblastoma multiforme.Cell death & disease · 2024Review
- CBX2 enhances the progression and TMZ chemoresistance of glioma via EZH2-mediated epigenetic silencing of PTEN expression.Frontiers in pharmacology · 2024Article
- Metformin and its potential influence on cell fate decision between apoptosis and senescence in cancer, with a special emphasis on glioblastoma.Frontiers in oncology · 2024Review
- Metformin use is associated with longer survival in glioblastoma patients with MGMT gene silencing.Journal of neuro-oncology · 2023Article
- CMA mediates resistance in breast cancer models.Cancer cell international · 2023Article
- 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
- miR-1297 sensitizes glioma cells to temozolomide (TMZ) treatment through targeting adrenomedullin (ADM).Journal of translational medicine · 2022Article
- Effects of Metformin as Add-On Therapy against Glioblastoma: An Old Medicine for Novel Oncology Therapeutics.Cancers · 2022Article
- Necrotic reshaping of the glioma microenvironment drives disease progression.Acta neuropathologica · 2022Review
- Hypoxia Promotes Glioma Stem Cell Proliferation by Enhancing the 14-3-3Journal of immunology research · 2022Article
- Review
- Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook.Cancers · 2021Review
- Imaging Metformin Efficacy as Add-On Therapy in Cells and Mouse Models of Human EGFR Glioblastoma.Frontiers in oncology · 2021Article
- Molecular and Cellular Complexity of Glioma. Focus on Tumour Microenvironment and the Use of Molecular and Imaging Biomarkers to Overcome Treatment Resistance.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is a key driver of tumor adaptation promoting tumor progression and resistance to therapy. Hypoxia related pathways might represent attractive targets for the treatment of Glioblastoma Multiforme (GBM), that up to date is characterized by a poor prognosis. Primary aim of this study was to investigate the role of hypoxia and hypoxia-related modifications in the effect of temozolomide (TMZ) given alone or in association with the antidiabetic agent Metformin (MET) or the PI3K/mTOR blocker, BEZ235. The study was conducted in the TMZ responsive U251 and resistant T98 GBM cells. Our results showed that during hypoxia, TMZ plus MET reduced viability of U251 cells affecting also CD133 and CD90 expressing cells. This effect was associated with a reduction of HIF-1α activity, VEGF release and AKT activation. In T98 TMZ-resistant cells, TMZ plus MET exerted similar effects on HIF-1α. However, in this cell line, TMZ plus MET failed to reduce CD133 positive cells and AKT phosphorylation. Nevertheless, the administration of the dual PI3K/mTOR inhibitor BEZ235 potentiated the effect of TMZ plus MET on cell viability, inducing a pro-apoptotic phenotype during hypoxic condition also in T98 cells, suggesting the block of the PI3K/AKT/mTOR pathway as a complementary target to further overcome GBM resistance during hypoxia. In conclusion, we proposed TMZ plus MET as suitable treatment to revert TMZ-resistance also during hypoxia, an effect potentiated by the inhibition of PI3K/mTOR axis.
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