Targeting miR‑155‑5p and miR‑221‑3p by Peptide Nucleic Acids Induces caspase‑3 Activation and Apoptosis in temozolomide‑resistant T98G Glioma Cells

Int J Oncol. 2019 Jul;55(1):59-68. doi: 10.3892/ijo.2019.4810. Epub 2019 May 23.

Abstract

The present study investigated the effects of the combined treatment of two peptide nucleic acids (PNAs), directed against microRNAs involved in caspase‑3 mRNA regulation (miR‑155‑5p and miR‑221‑3p) in the temozolomide (TMZ)‑resistant T98G glioma cell line. These PNAs were conjugated with an octaarginine tail in order to obtain an efficient delivery to treated cells. The effects of singularly administered PNAs or a combined treatment with both PNAs were examined on apoptosis, with the aim to determine whether reversion of the drug‑resistance phenotype was obtained. Specificity of the PNA‑mediated effects was analyzed by reverse transcription‑quantitative polymerase‑chain reaction, which demonstrated that the effects of R8‑PNA‑a155 and R8-PNA-a221 anti‑miR PNAs were specific. Furthermore, the results obtained confirmed that both PNAs induced apoptosis when used on the temozolomide‑resistant T98G glioma cell line. Notably, co‑administration of both anti‑miR‑155 and anti‑miR‑221 PNAs was associated with an increased proapoptotic activity. In addition, TMZ further increased the induction of apoptosis in T98G cells co‑treated with anti‑miR‑155 and anti‑miR‑221 PNAs.

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Drug Synergism
  • Enzyme Activation / drug effects
  • Glioma / drug therapy*
  • Glioma / enzymology
  • Glioma / genetics*
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • Peptide Nucleic Acids / genetics
  • Peptide Nucleic Acids / pharmacology*
  • Temozolomide / pharmacology*

Substances

  • Antineoplastic Agents, Alkylating
  • MIRN155 microRNA, human
  • MIRN221 microRNA, human
  • MicroRNAs
  • Peptide Nucleic Acids
  • CASP3 protein, human
  • Caspase 3
  • Temozolomide