International Journal of Molecular and Cellular Medicine (IJMCM)

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 β-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 β-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 β-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/β-catenin signaling pathway may represent a promising adjuvant strategy to improve therapeutic outcomes in GBM.