@Article{or.2026.079463,
AUTHOR = {Boqi Zhou, Liping Shen, Xiaojie Lu},
TITLE = {Baclofen Inhibits Glioma Proliferation via the MEK/ERK/CREB Pathway},
JOURNAL = {Oncology Research},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/or/online/detail/26569},
ISSN = {1555-3906},
ABSTRACT = {<b>Objectives:</b> Gamma-aminobutyric acid type B (GABAB) receptors are involved in tumor progression, and baclofen exerts broad-spectrum antitumor effects in various cancers. Nevertheless, its specific function and underlying molecular mechanisms in glioma are still largely unclear. This study aimed to evaluate the effects of baclofen on glioma cells and elucidate the associated signaling pathways. <b>Methods:</b> The antitumor effects of baclofen were evaluated in glioma cell lines, and its underlying molecular mechanisms were explored using transcriptome sequencing integrated with Western blotting. The <i>in vivo</i> antitumor efficacy of baclofen was further verified in animal models. <b>Results:</b> <i>In vitro</i> functional assays revealed that baclofen inhibits the proliferation, migration, and invasion of glioma cells in a dose-dependent manner. Transcriptomic sequencing combined with Western blot validation demonstrated that these effects may be mediated by GABAB receptors, leading to suppressed phosphorylation of key molecules in the Mitogen-activated protein kinase kinase (MEK)/Extracellular regulated protein kinases (ERK) pathway, and consequently reduced phosphorylation of the downstream transcription factors cAMP-response element binding protein (CREB) and Fos Proto-Oncogene (FOS). Furthermore, baclofen regulates the epithelial-mesenchymal transition (EMT-like) program. All these effects were abolished by co-treatment with the specific GABAB antagonist CGP35348. <i>In vivo</i> experiments using a subcutaneous glioma xenograft model further verified that the continuous use of baclofen in experimental animals also demonstrated certain anti-tumor effects. <b>Conclusion:</b> Collectively, these findings demonstrate that baclofen exerts anti-glioma effects through GABAB receptor-mediated inhibition of the MEK/ERK/CREB signaling axis and modulation of the EMT-like pathway, thereby highlighting the potential of baclofen as a therapeutic agent for glioma.},
DOI = {10.32604/or.2026.079463}
}