en Neurosciences Neurosciences Original Article Original Article <p style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="line-height:107%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black"><span style="font-size:12px;"><span style="font-family:Tahoma;">Glioblastoma (GBM) remains the most aggressive brain tumor, characterized by rapid proliferation and resistance to temozolomide (TMZ). Emerging evidence suggests that the Wnt signaling through stabilization of &beta;-catenin and expression of the non-canonical ligand Wnt5a, has been implicated in the maintenance of GBM. Cannabidiol (CBD) has emerged as a potential adjuvant that may modulate these pathways to overcome chemoresistance. Therefor we determined human U87-MG cells treatment with Different concentration of CBD and TMZ determined in 24, 48, and 72hours. Cell viability, combination index, IC₅₀and IC₅ were assed with MTT assay. Protein levels of &beta;-catenin, Wnt5a, and AXIN1 were evaluated using western blotting and immunofluorescence assay. Treatment with CBD in combination TMZ significantly reduced U87-MG cell viability in a time and dose dependent manner. The combination index analysis indicated a synergistic interaction between CBD and TMZ, particularly at 48 and72 hours. IC₅₀values decreased significantly enhanced co administration compared to mono therapy, suggesting enhanced chemosensitivity. Western blotting and IF results revealed that down regulation of &beta;-catenin and Wnt5a by increasing AXIN1 expression, supporting modulation of canonical and non-canonical Wnt signaling pathways. These findings demonstrate that CBD potentiates the cytotoxic effects of TMZ in glioblastoma cells by interfering with Wnt/&beta;-catenin signaling pathway may represent a promising adjuvant strategy to improve therapeutic outcomes in GBM.</span></span> </span></span></span></span><span style="color:black"></span></span></span></span></p> <br> &nbsp; Glioblastoma multiform, Temozolomide, Cannabidiol, adjuvant therapy, Wnt/β-catenin signaling, β-catenin, Wnt5a, AXIN1 0 0 http://ijmcmed.org/browse.php?a_code=A-10-9073-1&slc_lang=en&sid=1 Aliakbar Rajabzadeh aa.rajabzadeh@mubabol.ac.ir 100319475328460037348 100319475328460037348 Yes Department of Anatomy, Embryology, and Histology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran