ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2022
Regorafenib Reverses Temozolomide-Induced CXCL12/CXCR4 Signaling and Triggers Apoptosis Mechanism in Glioblastoma.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- IL-37 drives temozolomide resistance in glioblastoma via MAPK pathway activation.Oncology letters · 2026Article
- A mechanobiology-driven cell-derived ECM bioink for engineering 3D glioblastoma tumor microenvironment models.Theranostics · 2026Article
- Current evidence and challenges of multitarget anti-angiogenic agents for glioblastoma: Results from clinical trials.iScience · 2025Review
- Kinase-Targeted Therapies for Glioblastoma.International journal of molecular sciences · 2025Review
- Innovative dual-gene delivery platform using miR-124 and PD-1 via umbilical cord mesenchymal stem cells and exosome for glioblastoma therapy.Journal of experimental & clinical cancer research : CR · 2025Article
- A Review of FDA-Approved Multi-Target Angiogenesis Drugs for Brain Tumor Therapy.International journal of molecular sciences · 2025Review
- Regorafenib and glioblastoma: a literature review of preclinical studies, molecular mechanisms and clinical effectiveness.Expert reviews in molecular medicine · 2024Review
- Overcoming multidrug resistance by reversan and exterminating glioblastoma and glioblastoma stem cells by delivering drug-loaded nanostructure hybrid lipid capsules (nHLCs).Drug delivery and translational research · 2024Article
- Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024Review
- Revisiting the potential of regulated cell death in glioma treatment: a focus on autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis, immunogenic cell death, and the crosstalk between them.Frontiers in oncology · 2024Review
- Identification of molecular subtypes and a risk model based on inflammation-related genes in patients with low grade glioma.Heliyon · 2023Article
- Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner.BMC cancer · 2023Article
- The Recent Research Progress of NF-κB Signaling on the Proliferation, Migration, Invasion, Immune Escape and Drug Resistance of Glioblastoma.International journal of molecular sciences · 2023Review
- Adverse Toxic Effects of Tyrosine Kinase Inhibitors on Non-Target Zebrafish Liver (ZFL) Cells.International journal of molecular sciences · 2023Article
- A Novel Isotope-labeled Small Molecule Probe CC12 for Anti-glioma via Suppressing LYN-mediated Progression and Activating Apoptosis Pathways.International journal of biological sciences · 2023Article
- Studies on Biological and Molecular Effects of Small-Molecule Kinase Inhibitors on Human Glioblastoma Cells and Organotypic Brain Slices.Life (Basel, Switzerland) · 2022Article
- Hyperforin Suppresses Oncogenic Kinases and Induces Apoptosis in Colorectal Cancer Cells.In vivo (Athens, Greece)Article
- Humanized PD-1 Knock-in Mice Reveal Nivolumab's Inhibitory Effects on Glioblastoma Tumor ProgressionIn vivo (Athens, Greece)Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temozolomide (TMZ) monotherapy is known to be insufficient for resistant/relapsed glioblastoma (GBM), thus seeking a sensitization agent for TMZ is necessary. It was found that regorafenib may improve the overall survival of relapsed GBM patients. We aimed to discover whether regorafenib can enhance the anti-GBM effects of TMZ, and elucidate underlying mechanism. Our analysis of The Cancer Genome Atlas database revealed that the increased expression of CXCR4 is linked to poor survival of GBM patients. Additionally, TMZ treatment may trigger CXCR4/CXCL12 axis of GBM. We used two GBM cell lines, two primary GBM cells, and animal model to identify underlying mechanism and treatment efficacy of regorafenib combined with TMZ by cytotoxicity, apoptosis, reporter gene and invasion/migration assays, chemokine array, Western blotting, MRI, microarray, and immunohistochemistry. We observed that the chemokine CXCL-12 and its receptor CXCR4 regulate the resistance to TMZ, whereas the inhibition of CXCL-12/CXCR4 signaling sensitizes GBM cells to TMZ. The TMZ-induced CXCL-12/CXCR4 signaling, phosphor-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB), and NF-κB-related proteins can effectively diminish when combining with regorafenib. Regorafenib significantly enhanced the TMZ-induced extrinsic/intrinsic apoptotic pathways, and facilitated the suppression of invasion and migration potential in GBM. Orthotopic tumor experiments demonstrated tumor size reduction and prolonged survival in combination group even with half-dose of TMZ. Our findings provide promising evidence that regorafenib may sensitize GBM to TMZ treatment through inhibition of the CXCL12/CXCR4/ERK/NF-κB signaling.
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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.