Specific COX-2 inhibitor, NS-398, suppresses cellular proliferation and induces apoptosis in human hepatocellular carcinoma cells

Int J Oncol. 2003 Jul;23(1):113-9.


Cyclooxygenase (COX-2) has been recently suggested to play a role in hepatocarcinogenesis. However, the exact pathway by which COX-2 affects the growth of hepatocellular carcinoma (HCC) is not clear. This study investigated the effects of a specific COX-2 inhibitor, NS-398, on the cell proliferation and apoptosis of COX-2-expressing and non-expressing HCC cell lines. In addition, the modulatory effect of NS-398 on apoptosis-regulating gene expression was examined. Semi-quantitative/quantitative reverse transcription-polymerase chain reaction and Western blot showed that Hep3B and HKCI-4 cells expressed COX-2 mRNA and protein, but HepG2 cells did not. NS-398 suppressed cell proliferation and induced apoptosis in the two COX-2-expressing cell lines in a dose-dependent manner, but not in HepG2 cells. Fas ligand mRNA and protein expression were increased by the treatment with NS-398 (10 micro M) in COX-2-expressing cell lines. The expressions of Fas and Bcl-2 family genes (Bax, Bcl-2, Bcl-xL, Bcl-xS) were not affected by NS-398 treatment in all three cell lines. In conclusion, specific COX-2 inhibitor suppresses cell proliferation and induces apoptosis in HCC cell lines that express COX-2. Our finding suggests that COX-2 inhibition may offer a new approach for HCC chemoprevention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / pharmacology
  • Apoptosis*
  • Blotting, Western
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / pathology*
  • Cell Division
  • Cell Line
  • Cell Line, Tumor
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein
  • Fluorescent Dyes / pharmacology
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology*
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins
  • Nitrobenzenes / pharmacology*
  • Prostaglandin-Endoperoxide Synthases
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology*


  • Annexin A5
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Fluorescent Dyes
  • Isoenzymes
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nitrobenzenes
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases