Background/Aims
Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular
carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being
associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism
regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in
selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. Methods: After treatment with
NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 μM), the growth
inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel
analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription
polymerase chain reactions. Results: NS-398 inhibited the growth of hepatoma cells by an amount dependent
on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the
sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the
expression of the survivin gene in a concentration- and time-dependent manner. Conclusions: Survivin was
down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in
a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via
suppression of survivin in HCC. (Korean J Hepatol 2008;14:351-359)
