ArticleMolecular cancer therapeutics2015
Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 52 citations in OpenAlex.
- Engineered Exosomes for Delivery of Mir-423-5p to Improve Radiation Sensitivity by Inhibiting MAP7D1 in Esophageal Cancer.Annals of surgical oncology · 2026Article
- Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models.The Journal of clinical investigation · 2026Article
- Endogenous inhibitors of PP2A activate oncogenic and DNA damage response kinases in glioblastoma.Cancer letters · 2026Article
- A Phase 0 Window of Opportunity Trial of LB100, a Protein Phosphatase 2A Inhibitor, in Patients with Recurrent Gliomas.medRxiv : the preprint server for health sciences · 2025Article
- Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- A Small Molecule Inhibitor of Leucine Carboxyl Methyltransferase-1 Inhibits Cancer Cell Survival.Frontiers in drug discovery · 2024Article
- PP2Ac Deficiency Enhances Tumor Immunogenicity by Activating STING-Type I Interferon Signaling in Glioblastoma.Cancer research · 2023Article
- PME-1 sensitizes glioblastoma cells to oxidative stress-induced cell death by attenuating PP2A-B55α-mediated inactivation of MAPKAPK2-RIPK1 signaling.Cell death discovery · 2023Article
- Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis.International journal of molecular sciences · 2023Review
- The Pivotal Role of Protein Phosphatase 2A (PP2A) in Brain Tumors.International journal of molecular sciences · 2022Review
- Radiotherapy modulates tumor cell fate decisions: a review.Radiation oncology (London, England) · 2022Review
- Review
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- Inhibiting PP2A Upregulates B7-H3 Expression and Potentially Increases the Sensitivity of Malignant Meningiomas to Immunotherapy by Proteomics.Pathology oncology research : POR · 2022Article
- Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer.Molecular cancer therapeutics · 2021Article
- The Radiosensitizing Effect of AZD0530 in Glioblastoma and Glioblastoma Stem-Like Cells.Molecular cancer therapeutics · 2021Article
- Review of PP2A Tumor Biology and Antitumor Effects of PP2A Inhibitor LB100 in the Nervous System.Cancers · 2021Review
- MiR-1297 negatively regulates metabolic reprogramming in glioblastoma via repressing KPNA2.Human cell · 2020Article
- High STRN Expression Promotes HCC Invasion and Migration but Not Cell Proliferation or Apoptosis through Facilitating Epithelial-Mesenchymal Transition.BioMed research international · 2020Article
- Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression.Redox biology · 2019Review
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Protein phosphatase 2A (PP2A) is a tumor suppressor whose function is lost in many cancers. An emerging, though counterintuitive, therapeutic approach is inhibition of PP2A to drive damaged cells through the cell cycle, sensitizing them to radiotherapy. We investigated the effects of PP2A inhibition on U251 glioblastoma cells following radiation treatment in vitro and in a xenograft mouse model in vivo. Radiotherapy alone augmented PP2A activity, though this was significantly attenuated with combination LB100 treatment. LB100 treatment yielded a radiation dose enhancement factor of 1.45 and increased the rate of postradiation mitotic catastrophe at 72 and 96 hours. Glioblastoma cells treated with combination LB100 and radiotherapy maintained increased γ-H2AX expression at 24 hours, diminishing cellular repair of radiation-induced DNA double-strand breaks. Combination therapy significantly enhanced tumor growth delay and mouse survival and decreased p53 expression 3.68-fold, compared with radiotherapy alone. LB100 treatment effectively inhibited PP2A activity and enhanced U251 glioblastoma radiosensitivity in vitro and in vivo. Combination treatment with LB100 and radiation significantly delayed tumor growth, prolonging survival. The mechanism of radiosensitization appears to be related to increased mitotic catastrophe, decreased capacity for repair of DNA double-strand breaks, and diminished p53 DNA-damage response pathway activity.
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