Specific COX-2 inhibitor, NS-398, suppresses cellular proliferation and induces apoptosis in human hepatocellular carcinoma cells.
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.
Cheng
Alfred S L
AS
Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, P.R. China. alfredcheng@cuhk.edu.hk
Chan
Henry L Y
HL
Leung
Wai K
WK
Wong
Nathalie
N
Johnson
Philip J
PJ
Sung
Joseph J Y
JJ
D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology*
D017304:Annexin A5; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005456:Fluorescent Dyes; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases