Korean J Hepatol.  2008 Sep;14(3):351-359. 10.3350/kjhep.2008.14.3.351.

Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor

• Song IH
• Kim DW
• Shin KC
• Shin HD
• Yun SY
• Kim SB
• Shin JE
• Kim HJ
• Kim EY

• KMID: 1381465
• DOI: http://doi.org/10.3350/kjhep.2008.14.3.351

Abstract

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 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.

Keyword

Carcinoma, hepatocellular; Survivin; Cyclooxygenase-2 (COX-2); COX-2 inhibitor, Apoptosis

MeSH Terms

Carcinoma, Hepatocellular/enzymology/*metabolism/pathology
Cell Line, Tumor
Cell Proliferation/drug effects
Cyclooxygenase 2 Inhibitors/chemistry/*pharmacology
G1 Phase
Humans
Liver Neoplasms/enzymology/*metabolism/pathology
Microtubule-Associated Proteins/*antagonists & inhibitors/metabolism
Neoplasm Proteins/*antagonists & inhibitors/metabolism
Nitrobenzenes/chemistry/*pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Sulfonamides/chemistry/*pharmacology
Time Factors