[Diclofenac suppresses hepatoma cell proliferation and promotes cyclooxygenase-2 mRNA expression].
OBJECTIVE
To investigate the effects of cyclooxygenase inhibitor diclofenac on the proliferation and cyclooxygenase-2 (COX-2) mRNA expression of cultured hepatocellular carcinoma cell lines HepG2, Hep3B and human hepatocellular cell line QSG-7701.


METHODS
After exposure to diclofenac at various concentrations (10-200 micromol/L) for 24, 48 and 72 h, the cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay and mRNA expression determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Diclofenac exposure for 24, 48 and 72 h significantly inhibited HepG2 and Hep3B cell proliferation in a concentration-dependent manner, with inhibition rate of 40.47% and 54.49% after 48 h exposure to 50 micromol/L diclofenac and IC50 of 70.54 and 48.39 micromol/L, respectively. A much weaker antiproliferative effect on QSG-7701 cells was shown, with IC50 of 189.91 micromol/L after 48-hour exposure to diclofenac. RT-PCR detected COX-2 mRNA in HepG2 and Hep3B cells, but hardly in QSG-7701 cells. Treatment with diclofenac or 5-Fu resulted in elevated COX-2 mRNA expression both in HepG2 and Hep3B cells.


CONCLUSIONS
Diclofenac can specifically inhibit the proliferation of COX-2-expressing HepG2 and Hep3B cells, and induce up-regulation of COX-2 mRNA expression, which indicates the important role of COX-2 in the proliferation of hepatoma cells.
Chen
Na-Na
NN
College of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. yxbyjs@fimmu.com
Wu
Shu-Guang
SG
D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D004008:Diclofenac; D051546:Cyclooxygenase 2