A methylated oligonucleotide induced methylation of GSTP1 promoter and suppressed its expression in A549 lung adenocarcinoma cells

Cancer Lett. 2004 Aug 30;212(2):211-23. doi: 10.1016/j.canlet.2004.03.001.

Abstract

Glutathione S-transferase P1 (GSTP1) belongs to xenobiotic enzymes, and is supposed to contribute to chemoresistance. Though it was reported that GSTP1 gene is suppressed by cytosine-guanine (CpG) island methylation of its promoter, this promoter is not strongly methylated and GSTP1 protein is highly expressed in lung cancer. We intended to induce methylation of GSTP1 CpG island by using a methylated sense oligonucleotide complementary to this region. When we transduced the methylated oligonucleotides to A549 lung adenocarcinoma cells, methylation of the GSTP1 promoter and reduction of GSTP1 expression was induced, cell viability was reduced; however, chemoresistance against cisplatin has not clearly changed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Base Sequence
  • Cell Line, Tumor
  • Cell Survival
  • Cisplatin / pharmacology
  • CpG Islands
  • Cytosine / chemistry
  • DNA Methylation*
  • DNA Primers / chemistry
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Genetic Techniques*
  • Glutathione Transferase / genetics*
  • Guanine / chemistry
  • Humans
  • Immunoblotting
  • Models, Genetic
  • Molecular Sequence Data
  • Oligonucleotides / genetics*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • RNA, Small Interfering
  • Time Factors
  • Transfection

Substances

  • DNA Primers
  • Oligonucleotides
  • RNA, Small Interfering
  • Guanine
  • Cytosine
  • Glutathione Transferase
  • Cisplatin