ArticleOncotarget2017
Axitinib induces senescence-associated cell death and necrosis in glioma cell lines: The proteasome inhibitor, bortezomib, potentiates axitinib-induced cytotoxicity in a p21(Waf/Cip1) dependent manner.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Discovery of a novel VEGFR2 inhibitor using integrated structure-based docking study and functional validation: potential applications in targeted cancer therapy.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- Kinase-Targeted Therapies for Glioblastoma.International journal of molecular sciences · 2025Review
- A Review of FDA-Approved Multi-Target Angiogenesis Drugs for Brain Tumor Therapy.International journal of molecular sciences · 2025Review
- N-Acetyl-L-Cysteine (NAC) Blunts Axitinib-Related Adverse Effects in Preclinical Models of Glioblastoma.Cancer medicine · 2024Article
- Article
- The in vitro dynamics of pseudo-vascular network formation.British journal of cancer · 2024Article
- Improving the power of drug toxicity measurements by quantitative nuclei imaging.Cell death discovery · 2024Article
- Exploring the multifaceted antitumor activity of axitinib in lung carcinoids.Frontiers in endocrinology · 2024Article
- Viability of Glioblastoma Cells and Fibroblasts in the Presence of Imidazole-Containing Compounds.International journal of molecular sciences · 2022Article
- Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas.Frontiers in oncology · 2022Article
- Antiangiogenic Properties of Axitinib versus Sorafenib Following Sunitinib Resistance in Human Endothelial Cells-A View towards Second Line Renal Cell Carcinoma Treatment.Biomedicines · 2021Article
- Cellular senescence in cancer: from mechanisms to detection.Molecular oncology · 2021Review
- Pyrazolo[3,4-Brain sciences · 2021Article
- Review
- The Paradoxical Role of Cellular Senescence in Cancer.Frontiers in cell and developmental biology · 2021Review
- ATM at the crossroads of reactive oxygen species and autophagy.International journal of biological sciences · 2021Review
- Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer.Frontiers in cardiovascular medicine · 2021Review
- Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma is associated with a poor overall survival despite new treatment advances. Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma.Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by γ-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines. Moreover, we found that p21(Waf1/Cip1) increased levels correlates with induction of ROS and senescence-associated cell death in U87 and T98 cell lines, which are reverted by N-acetyl cysteine pretreatment. Conversely, U251 cell line showed a resistant phenotype in response to axitinib treatment, as evidenced by cell cycle arrest but no sign of cell death.The combinatorial use of axitinib with other therapies, with the aim of inhibiting multiple signaling pathways involved in tumor growth, can increase the efficiency of this TKI. Thus, we addressed the combined effects of axitinib with no toxic doses of the proteasome inhibitor bortezomib on the growth of U87 and T98 axitinib-sensitive and axitinib-resistant U251 cell lines. Compared to single treatments, combined exposure was more effective in inhibiting cell viability of all glioma cell lines, although with different cell death modalities. The regulation of key DDR and cell cycle proteins, including Chk1, γ-H2AX and p21(Waf1/Cip1) was also studied in glioma cell lines.Collectively, these findings provide new perspectives for the use of axitinib in combination with Bortezomib to overcome the therapy resistance in gliomas.
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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.