Molecular Characterization of the Dual Effect of the GPER Agonist G-1 in Glioblastoma
-
Published:2022-11-18
Issue:22
Volume:23
Page:14309
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Hirtz Alex, Bailly Yann, Rech Fabien, Pierson Julien, Dumond HélèneORCID, Dubois-Pot-Schneider HélèneORCID
Abstract
Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite conventional treatment, consisting of a chirurgical resection followed by concomitant radio–chemotherapy, the 5-year survival rate is less than 5%. Few risk factors are clearly identified, but women are 1.4-fold less affected than men, suggesting that hormone and particularly estrogen signaling could have protective properties. Indeed, a high GPER1 (G-protein-coupled estrogen receptor) expression is associated with better survival, especially in women who produce a greater amount of estrogen. Therefore, we addressed the anti-tumor effect of the GPER agonist G-1 in vivo and characterized its molecular mechanism of action in vitro. First, the antiproliferative effect of G-1 was confirmed in a model of xenografted nude mice. A transcriptome analysis of GBM cells exposed to G-1 was performed, followed by functional analysis of the differentially expressed genes. Lipid and steroid synthesis pathways as well as cell division processes were both affected by G-1, depending on the dose and duration of the treatment. ANGPTL4, the first marker of G-1 exposure in GBM, was identified and validated in primary GBM cells and patient samples. These data strongly support the potential of G-1 as a promising chemotherapeutic compound for the treatment of GBM.
Funder
Cancéropole University of Lorraine
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference52 articles.
1. The 2021 WHO Classification of Tumors of the Central Nervous System: A Summary;Neuro-Oncology,2021 2. Grochans, S., Cybulska, A.M., Simińska, D., Korbecki, J., Kojder, K., Chlubek, D., and Baranowska-Bosiacka, I. (2022). Epidemiology of Glioblastoma Multiforme-Literature Review. Cancers, 14. 3. Hirtz, A., Lebourdais, N., Thomassin, M., Rech, F., Dumond, H., and Dubois-Pot-Schneider, H. (2022). Identification of Gender- and Subtype-Specific Gene Expression Associated with Patient Survival in Low-Grade and Anaplastic Glioma in Connection with Steroid Signaling. Cancers, 14. 4. Hirtz, A., Lebourdais, N., Rech, F., Bailly, Y., Vaginay, A., Smaïl-Tabbone, M., Dubois-Pot-Schneider, H., and Dumond, H. (2021). GPER Agonist G-1 Disrupts Tubulin Dynamics and Potentiates Temozolomide to Impair Glioblastoma Cell Proliferation. Cells, 10. 5. Localisation of GPR30, a Novel G Protein-Coupled Oestrogen Receptor, Suggests Multiple Functions in Rodent Brain and Peripheral Tissues;J. Endocrinol.,2009
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|