Effect of cyclooxygenase-2 antisense oligodeoxyribonucleotides in A-549 lung cancer cells

Anticancer Res. 2004 Nov-Dec;24(6):3789-94.

Abstract

Background: Cyclooxygenase (COX)-2 is overexpressed in several tumor entities and seems to play a key role in carcinogenesis. This makes it a potential target in cancer therapy.

Materials and methods: Twelve phosphorothioate-modified antisense oligonucleotides (asODNs) against six targets of COX-2 mRNA were transfected to A-549 lung carcinoma cells. COX-2 mRNA and protein levels were determined by quantitative RT-PCR and flow cytometry, respectively. Cell growth was assessed by measuring Alamar Blue reduction.

Results: The tested asODNs exhibited a range of activities. The most potent asODN reduced uninduced COX-2 mRNA to 66% and protein level to 75%, respectively. While this asODN did not influence cell growth, a 15% growth reduction was observed after transfection of another asODN which suppressed COX-2 mRNA to 71% and protein level to 84%.

Conclusion: The use of asODNs directed against COX-2 mRNA is a promising approach to inhibit COX-2 expression in tumor cells.

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / therapy*
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Cyclooxygenase 2
  • Flow Cytometry
  • Genetic Therapy
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / therapy*
  • Membrane Proteins
  • Oligodeoxyribonucleotides, Antisense / genetics*
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • Membrane Proteins
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases