Optimization of Epigenetic Modifier Drug Combination for Synergistic Effect against Glioblastoma Multiform Cancer Cell Lines

Cancer Invest. 2024 Apr;42(4):319-332. doi: 10.1080/07357907.2024.2345183. Epub 2024 May 2.

Abstract

Glioblastoma multiforme (GBM), is a frequent class of malignant brain tumors. Epigenetic therapy, especially with synergistic combinations is highly paid attention for aggressive solid tumors like GBM. Here, RSM optimization has been used to increase the efficient arrest of U87 and U251 cell lines due to synergistic effects. Cell lines were treated with SAHA, 5-Azacytidine, GSK-126, and PTC-209 individually and then RSM was used to find most effective combinations. Results showed that optimized combinations significantly reduce cell survival and induce cell cycle arrest and apoptosis in both cell lines. Expression of cyclin B1 and cyclin D1 were decreased while caspase3 increased expression.

Keywords: GBM; Glioblastoma multiform; combination therapy; epi-drug; response surface methodology.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis* / drug effects
  • Azacitidine / administration & dosage
  • Azacitidine / pharmacology
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Drug Synergism*
  • Epigenesis, Genetic* / drug effects
  • Glioblastoma* / drug therapy
  • Glioblastoma* / genetics
  • Glioblastoma* / pathology
  • Humans
  • Vorinostat / administration & dosage
  • Vorinostat / pharmacology

Substances

  • Azacitidine
  • Vorinostat
  • Cyclin D1