ArticleInternational journal of molecular sciences2023
Resveratrol Enhances Temozolomide Efficacy in Glioblastoma Cells through Downregulated MGMT and Negative Regulators-Related STAT3 Inactivation.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 23 citations in OpenAlex.
- Breaking adaptive oncogenic resistance in glioblastoma via targeting the EGFR-STAT3 axis.Medical oncology (Northwood, London, England) · 2026Review
- Folate-Targeted polymeric micelles enhance the anti-glioma efficacy of pterostilbene in an orthotopic rat model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Resveratrol and Curcumin in Stroke Therapy: From Experimental Evidence to Clinical Perspectives.Nutrients · 2026Review
- Flavonoid-modulated JAK-STAT signaling mitigates malignant transformation and drug resistance in breast tumors: A clinically relevant 3PM-guided innovation.Journal of advanced research · 2026Review
- Resveratrol as a Dual MAPK/STAT3 Inhibitor in Glioblastoma: Mutation-Dependent Therapeutic Efficacy.Life (Basel, Switzerland) · 2026Article
- Resveratrol and AG490 Overcome Glioblastoma Cells' Resistance to Monotherapy by Inhibiting JAK2/STAT3 Signalling Pathway.Cancers · 2026Article
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Targeting Nectin-4 sensitizes glioblastoma to temozolomide.Frontiers in pharmacology · 2026Article
- Multi-omics analysis identifies CCNB1 as a cell cycle factor driving glioblastoma progression and its inhibition by resveratrol.PloS one · 2026Article
- COL6A2: A Key Survival-Related Gene and Restricting Antitumor Immunity in Glioblastoma.Cancer science · 2025Article
- Resveratrol-mediated suppression of glioblastoma and glioma: targeting apoptosis, differentiation, and stem cell dynamics.Cancer cell international · 2025Review
- Oxidative Stress and Antioxidants in Glioblastoma: Mechanisms of Action, Therapeutic Effects and Future Directions.Antioxidants (Basel, Switzerland) · 2025Review
- GLUT3 enhances chemosensitivity in glioblastoma by transporting temozolomide and capecitabine.Cell death discovery · 2025Article
- Siramesine induced cell death of glioblastoma through inactivating the STAT3-MGMT signaling pathway.Journal of translational medicine · 2025Article
- Potential Therapeutic Appliances of Dietary Polyphenols: Resveratrol and Curcumin in Treatment of Gliomas.International journal of molecular sciences · 2025Review
- Glioblastoma multiforme: an updated overview of temozolomide resistance mechanisms and strategies to overcome resistance.Discover oncology · 2025Review
- ANG-Modified Liposomes Coloaded With α-Melittin and Resveratrol Induce Apoptosis and Pyroptosis in Glioblastoma Cells by Impeding Wnt/β-Catenin Signaling.CNS neuroscience & therapeutics · 2025Article
- The Potential Application of Resveratrol and Its Derivatives in Central Nervous System Tumors.International journal of molecular sciences · 2024Review
- Pyrimidine compounds BY4003 and BY4008 inhibit glioblastoma cells growth via modulating JAK3/STAT3 signaling pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Progress in the Treatment of Central Nervous System Diseases Based on Nanosized Traditional Chinese Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance blunts the efficacy of temozolomide (TMZ) in the treatment of glioblastoma (GBM). Elevated levels of O6-methylguanine-DNA methyltransferase (MGMT) and activation of signal transducer and of transcription 3 (STAT3) have been reported to correlate with GBM resistance to alkylator chemotherapy. Resveratrol (Res) inhibits tumor growth and improves drug chemosensitivity by targeting STAT3 signaling. Whether the combined therapy of TMZ and Res could enhance chemosensitivity against GBM cells and the underlying molecular mechanism remains to be determined. In this study, Res was found to effectively improve chemosensitivities of different GBM cells to TMZ, which was evaluated by CCK-8, flow cytometry, and cell migration assay. The combined use of Res and TMZ downregulated STAT3 activity and STAT3-regulated gene products, thus inhibited cell proliferation and migration, as well as induced apoptosis, accompanied by increased levels of its negative regulators: PIAS3, SHP1, SHP2, and SOCS3. More importantly, a combination therapy of Res and TMZ reversed TMZ resistance of LN428 cells, which could be related to decreased MGMT and STAT3 levels. Furthermore, the JAK2-specific inhibitor AG490 was used to demonstrate that a reduced MGMT level was mediated by STAT3 inactivation. Taken together, Res inhibited STAT3 signaling through modulation of PIAS3, SHP1, SHP2, and SOCS3, thereby attenuating tumor growth and increasing sensitivity to TMZ. Therefore, Res is an ideal candidate to be used in TMZ combined chemotherapy for GBM.
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