Pulsed and Discontinuous Electromagnetic Field Exposure Decreases Temozolomide Resistance in Glioblastoma by Modulating the Expression of O6-Methylguanine-DNA Methyltransferase, Cyclin-D1, and p53

Cancer Biother Radiopharm. 2021 Sep;36(7):579-587. doi: 10.1089/cbr.2020.3851. Epub 2020 Jul 9.

Abstract

Background: Glioblastoma is a malignant and very aggressive brain tumor with a poor prognosis. Despite having chemotherapy concomitant with surgery and/or radiation therapy, the median survival of glioblastoma-affected people is less than 1 year. Temozolomide (TMZ) is a chemotherapeutic used as a first line treatment of glioblastoma. Several studies have reported that resistance to TMZ due to overexpression of O6-methylguanine-DNA methyltransferase (MGMT) is the main reason for treatment failure. Several studies described that pulsed-electromagnetic field (EMF) exposure could induce cell death and influence gene expression. Materials and Methods: In this study the authors assessed the effects of EMF (50 Hz, 70 G) on cytotoxicity, cell migration, gene expression, and protein levels in TMZ-treated T98 and A172 cell lines. Results: In this study, the authors show that treatment with a combination of TMZ and EMF enhanced cell death and decreased the migration potential of T98 and A172 cells. The authors also observed overexpression of the p53 gene and downregulation of cyclin-D1 protein in comparison to controls. In addition, T98 cells expressed the MGMT protein following treatment, while the A172 cells did not express MGMT. Conclusion: Their data indicate that EMF exposure improved the cytotoxicity of TMZ on T98 and A172 cells and could partially affect resistance to TMZ in T98 cells.

Keywords: MGMT; P53; human glioblastoma cells (T98, A172); pulsed-electromagnetic field; temozolomide resistance.

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / radiation effects
  • Cyclin D2 / biosynthesis*
  • Cyclin D2 / genetics
  • DNA Modification Methylases / biosynthesis*
  • DNA Repair Enzymes / biosynthesis*
  • Drug Resistance, Neoplasm / radiation effects
  • Electromagnetic Fields
  • Gene Expression / drug effects
  • Gene Expression / radiation effects
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / therapy*
  • Humans
  • Magnetic Field Therapy*
  • Temozolomide / pharmacology*
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins / biosynthesis*

Substances

  • Antineoplastic Agents, Alkylating
  • CCND2 protein, human
  • Cyclin D2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide