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Peer-reviewedCC BY-NCInternational Journal of Molecular and Cellular Medicine

Synergistic effects of Temozolomide and Cannabidiol on the Wnt/β-Catenin Signaling Pathway in Glioblastoma

  • Leila Samiee1
  • Nasrin Nosratiyan1
  • Aliakbar Rajabzadeh2
  • Mohsen Pourghasem2
  • Fatemeh Esfandiary3
  1. 1Department of Anatomy, Embryology, and Histology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
  2. 2Department of Anatomy, Embryology, and Histology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
  3. 3Department of Anatomy and Cell Biology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
PDFCite

Abstract

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. Therefore, we determined human U87-MG cells treatment with different concentrations 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 that may represent a promising adjuvant strategy to improve therapeutic outcomes in GBM.

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Cite

BibTeXRIS
BibTeX
@article{samiee2026synergistic,
  title = {{Synergistic effects of Temozolomide and Cannabidiol on the Wnt/β-Catenin Signaling Pathway in Glioblastoma}},
  author = {Leila Samiee and Nasrin Nosratiyan and Aliakbar Rajabzadeh and Mohsen Pourghasem and Fatemeh Esfandiary},
  journal = {International Journal of Molecular and Cellular Medicine},
  year = {2026},
  month = jun,
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Synergistic effects of Temozolomide and Cannabidiol on the Wnt/β-Catenin Signaling Pathway in Glioblastoma
AU  - Leila Samiee
AU  - Nasrin Nosratiyan
AU  - Aliakbar Rajabzadeh
AU  - Mohsen Pourghasem
AU  - Fatemeh Esfandiary
PY  - 2026
DA  - 2026/06/01
JO  - International Journal of Molecular and Cellular Medicine
AB  - 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. Therefore, we determined human U87-MG cells treatment with different concentrations 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 that may represent a promising adjuvant strategy to improve therapeutic outcomes in GBM.
SN  - 2251-9637
SN  - 2251-9645
ER  -