Differential Characterization of Temozolomide-Resistant Human Glioma Cells

Int J Mol Sci. 2018 Jan 2;19(1):127. doi: 10.3390/ijms19010127.

Abstract

Glioblastoma multiforme (GBM) is the most common type of primary and malignant tumor occurring in the adult central nervous system. Temozolomide (TMZ) has been considered to be one of the most effective chemotherapeutic agents to prolong the survival of patients with glioblastoma. Many glioma cells develop drug-resistance against TMZ that is mediated by increasing O-6-methylguanine-DNA methyltransferase (MGMT) levels. The expression of connexin 43 was increased in the resistant U251 subline compared with the parental U251 cells. The expression of epithelial-mesenchymal transition (EMT)-associated regulators, including vimentin, N-cadherin, and β-catenin, was reduced in the resistant U251 subline. In addition, the resistant U251 subline exhibited decreased cell migratory activity and monocyte adhesion ability compared to the parental U251 cells. Furthermore, the resistant U251 subline also expressed lower levels of vascular cell adhesion molecule (VCAM)-1 after treatment with recombinant tumor necrosis factor (TNF)-α. These findings suggest differential characteristics in the drug-resistant GBM from the parental glioma cells.

Keywords: connexin 43; drug-resistant; glioblastoma; temozolomide.

MeSH terms

  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Connexin 43 / metabolism
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Dacarbazine / therapeutic use
  • Drug Resistance, Neoplasm* / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Monocytes / drug effects
  • Monocytes / pathology
  • Temozolomide
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Connexin 43
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Proteins
  • Vascular Cell Adhesion Molecule-1
  • Dacarbazine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide