[Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor].
OBJECTIVE
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 micrometer), 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.
Song
Il Han
IH
Department of Internal Medicine, Dankook University College of Medicine, Dankook University Hospital Institute of Medical Science, Cheonan, Korea. ihsong21@dankook.ac.kr
Kim
Dong Woo
DW
Shin
Ki Chul
KC
Shin
Hyun Duk
HD
Yun
Se Young
SY
Kim
Suk Bae
SB
Shin
Jung Eun
JE
Kim
Hong Ja
HJ
Kim
Eun Young
EY
D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016193:G1 Phase; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009578:Nitrobenzenes / Q000737:chemistry / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D000077022:Survivin; D013997:Time Factors
C107489:BIRC5 protein, human; D052246:Cyclooxygenase 2 Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; D000077022:Survivin; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide