Non-small cell lung cancer cycloxygenase activity and proliferation are inhibited by non-steroidal antiinflammatory drugs

Anticancer Res. Mar-Apr 1998;18(2A):775-82.

Abstract

The effects of non-steroidal antiinflammatory drugs (NSAIDs) on non-small cell lung cancer (NSCLC) were investigated. Arachidonic acid (AA) was metabolized to prostaglandin E2 (PGE2) in NSCLC cells. NSAIDs such as aspirin or indomethacin reduced PGE2 levels in NCI-H157 and H1264 cells, and the decrease caused by PGE2 was reversed by epidermal growth factor (EGF). By RT-PCR, both cyclooxygenase (COX)-1 and COX-2 mRNAs are detected in NCI-H157 and H1264 cells. By Northern analysis, COX-2 mRNA was induced by EGF and phorbol ester. By immunocytochemistry, COX-1 and COX-2 enzymes were localized to NSCLC tumors. Aspirin, indomethacin and ibuprofen decreased NSCLC growth in vitro. Aspirin and indomethacin inhibited proliferation of NSCLC xenografts in nude mice. These data suggest that COX enzymes may be important regulatory components of NSCLC.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Division / drug effects
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dinoprostone / biosynthesis
  • Female
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Tumor Cells, Cultured

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone