ArticleBMC cancer2019
Valproic acid-induced amphiregulin secretion confers resistance to temozolomide treatment in human glioma cells.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Harnessing Repurposed Drugs to Enhance Temozolomide Efficacy in Glioblastoma.Cancer reports (Hoboken, N.J.) · 2026Review
- Acquired vulnerability against EGF receptor inhibition in gastric cancer promoted by class I histone deacetylase inhibitor entinostat.Neoplasia (New York, N.Y.) · 2025Article
- Identifying Diffuse Glioma Subtypes Based on Pathway Enrichment Evaluation.Interdisciplinary sciences, computational life sciences · 2024Article
- Differential Impact of Valproic Acid onBiomedicines · 2024Article
- Valproic acid regulates the miR-155/Jarid2 axis by affecting miR-155 promoter methylation in glioma.Acta biochimica et biophysica Sinica · 2024Article
- CD45 inhibition in myeloid leukaemia cells sensitizes cellular responsiveness to chemotherapy.Annals of hematology · 2024Article
- Particulate matter facilitates amphiregulin-dependent lung cancer proliferation through glutamine metabolism.International journal of biological sciences · 2024Article
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Glutamine metabolism controls amphiregulin-facilitated chemoresistance to cisplatin in human chondrosarcoma.International journal of biological sciences · 2023Article
- A Selective Histone Deacetylase Inhibitor Induces Autophagy and Cell Death via SCNN1A Downregulation in Glioblastoma Cells.Cancers · 2022Article
- Cross-reactivity between histone demethylase inhibitor valproic acid and DNA methylation in glioblastoma cell lines.Frontiers in oncology · 2022Article
- The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma.International journal of molecular sciences · 2021Review
- Elevated XRCC5 expression level can promote temozolomide resistance and predict poor prognosis in glioblastoma.Oncology letters · 2021Article
- Valproic Acid: A Promising Therapeutic Agent in Glioma Treatment.Frontiers in oncology · 2021Review
- Knockdown of Amphiregulin Triggers Doxorubicin-Induced Autophagic and Apoptotic Death by Regulating Endoplasmic Reticulum Stress in Glioblastoma Cells.Journal of molecular neuroscience : MN · 2020Article
- Amphiregulin promotes cisplatin chemoresistance by upregulating ABCB1 expression in human chondrosarcoma.Aging · 2020Article
- Liver fluke granulin promotes extracellular vesicle-mediated crosstalk and cellular microenvironment conducive to cholangiocarcinoma.Neoplasia (New York, N.Y.) · 2020Article
- Selective Inhibition of HDAC1 by Macrocyclic Polypeptide for the Treatment of Glioblastoma: A Binding Mechanistic Analysis Based on Molecular Dynamics.Frontiers in molecular biosciences · 2020Article
- Valproic Acid Enhanced Apoptosis by Promoting Autophagy Via Akt/mTOR Signaling in Glioma.Cell transplantationArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGlioblastoma multiforme (GBM) is the most severe type of primary brain tumor with a high mortality rate. Although extensive treatments for GBM, including resection, irradiation, chemotherapy and immunotherapy, have been tried, the prognosis is still poor. Temozolomide (TMZ), an alkylating agent, is a front-line chemotherapeutic drug for the clinical treatment of GBM; however, its effects are very limited because of the chemoresistance. Valproic acid (VPA), an antiepileptic agent with histone deacetylase inhibitor activity, has been shown to have synergistic effects with TMZ against GBM. The mechanism of action of VPA on TMZ combination therapy is still unclear. Accumulating evidence has shown that secreted proteins are responsible for the cross talking among cells in the tumor microenvironment, which may play a critical role in the regulation of drug responses.
methodsTo understand the effect of VPA on secreted proteins in GBM cells, we first used the antibody array to analyze the cell culture supernatant from VPA-treated and untreated GBM cells. The results were further confirmed by lentivirus-mediated knockdown and exogenous recombinant administration.
resultsOur results showed that amphiregulin (AR) was highly secreted in VPA-treated cells. Knockdown of AR can sensitize GBM cells to TMZ. Furthermore, pretreatment of exogenous recombinant AR significantly increased EGFR activation and conferred resistance to TMZ. To further verify the effect of AR on TMZ resistance, cells pre-treated with AR neutralizing antibody markedly increased sensitivity to TMZ. In addition, we also observed that the expression of AR was positively correlated with the resistance of TMZ in different GBM cell lines.
conclusionsThe present study aimed to identify the secreted proteins that contribute to the modulation of drug response. Understanding the full set of secreted proteins present in glial cells might help reveal potential therapeutic opportunities. The results indicated that AR may potentially serve as biomarker and therapeutic approach for chemotherapy regimens in GBM.
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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.