MicroRNA-21 inhibition enhances in vitro chemosensitivity of temozolomide-resistant glioblastoma cells

Anticancer Res. 2012 Jul;32(7):2835-41.

Abstract

Background: Glioblastoma multiforme (GBM) is a form of highly malignant brain tumour. Temozolomide (TMZ) is the standard agent for GBM, but TMZ-resistance is common and accounts for many treatment failures. MicroRNA-21 (miR-21) is a non-coding RNA that plays critical roles in many biological processes in cancer, including chemoresistance. We investigated miR-21 expression and the effect of miR-21 inhibition in GBM with acquired TMZ resistance.

Materials and methods: Human GBM cell line D54MG was treated with TMZ chronically to develop a chemoresistant subclone. MiR-21 inhibition was achieved by transfection with anti-mir-21 oligonucleotide.

Results: Chronic TMZ exposure resulted in acquired TMZ-resistance and elevated miR-21 expression. Concomitant treatment with miR-21 inhibitor and TMZ resulted in a significantly higher apoptotic rate than TMZ treatment alone.

Conclusion: MiR-21 may have a potential for use as a biomarker of acquired TMZ resistance. MiR-21 inhibition can be further explored as a potential chemotherapy adjunct in the treatment of TMZ-resistant GBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Genetic Therapy
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / therapy*
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Oligonucleotides, Antisense / administration & dosage*
  • Oligonucleotides, Antisense / genetics
  • Temozolomide
  • Transfection

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • MIRN21 microRNA, human
  • MicroRNAs
  • Oligonucleotides, Antisense
  • Dacarbazine
  • Temozolomide