ArticlePloS one2017
Inhibition of NF-κB Pathway and Modulation of MAPK Signaling Pathways in Glioblastoma and Implications for Lovastatin and Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) Combination Therapy.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Pooled it
- Pooled it
- Chaetocin enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis by enhancing DR5 stabilization and reactive oxygen species generation in human glioblastoma cells.International journal of oncology · 2025Article
- Lipid-lowering drugs and cancer: an updated perspective.Pharmacological reports : PR · 2024Review
- Bidirectional Mendelian Randomization of Causal Relationship between Inflammatory Cytokines and Different Pathological Types of Lung Cancer.Journal of Cancer · 2024Article
- Article
- Lovastatin inhibits erythroleukemia progression through KLF2-mediated suppression of MAPK/ERK signaling.BMC cancer · 2023Article
- Nano-TRAIL: a promising path to cancer therapy.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Kaempferol sensitizes tumor necrosis factor-related apoptosis-inducing ligand-resistance chronic myelogenous leukemia cells to apoptosis.Molecular biology reports · 2022Article
- Dual role of ERK2/NF-κB signaling in TRAIL sensitivity.American journal of cancer research · 2022Article
- The multifaceted NF-kB: are there still prospects of its inhibition for clinical intervention in pediatric central nervous system tumors?Cellular and molecular life sciences : CMLS · 2021Review
- Overcoming TRAIL Resistance for Glioblastoma Treatment.Biomolecules · 2021Review
- Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges.Frontiers in immunology · 2021Review
- CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells.Journal of cell communication and signaling · 2020Article
- Review
- Receptor-Targeted Glial Brain Tumor Therapies.International journal of molecular sciences · 2018Review
- GroEL/ES mediated the in vivo recovery of TRAIL inclusion bodies in Escherichia coli.Scientific reports · 2018Article
- Pomegranate Juice Prevents the Formation of Lung Nodules Secondary to Chronic Cigarette Smoke Exposure in an Animal Model.Oxidative medicine and cellular longevity · 2017Article
- Effects of Lovastatin on Brain Cancer Cells.Cell transplantationReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma is a common malignant brain tumor and it is refractory to therapy because it usually contains a mixture of cell types. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has been shown to induce apoptosis in a range of tumor cell types. Previously, we found that two human glioblastoma cell lines are resistant to TRAIL, while lovastatin sensitizes these glioblastoma cells to TRAIL-induced cell death. In this study, we investigated the mechanisms underlying the TRAIL-induced apoptosis in human glioblastoma cell lines by lovastatin. Furthermore, we have confirmed the anti-tumor effect of combination therapy with lovastatin and TRAIL in the subcutaneous brain tumor model. We showed that lovastatin significantly up-regulated the expression of death receptor 5 (DR5) in glioblastoma cell lines as well as in tumor-bearing mice with peri-tumoral administration of lovastatin. Further study in glioblastoma cell lines suggested that lovastatin treatment could inhibit NF-κB and Erk/MAPK pathways but activates JNK pathway. These results suggest that lovastatin sensitizes TRAIL-induced apoptosis by up-regulation of DR5 level via NF-κB inactivation, but also directly induces apoptosis by dysregulation of MAPK pathway. Our in vivo study showed that local peri-tumoral co-injection of lovastatin and TRAIL substantially reduced tumor growth compared with single injection of lovastatin or TRAIL in subcutaneous nude mice model. This study suggests that combined treatment of lovastatin and TRAIL is a promising therapeutic strategy to TRAIL-resistant glioblastoma.
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