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

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.

• Authors: Il Han Song, Dong Woo Kim, Ki Chul Shin, Hyun Duk Shin, Se Young Yun, Suk Bae Kim, Jung Eun Shin, Hong Ja Kim, Eun Young Kim
• Journal: The Korean journal of hepatology (Korean J Hepatol) Vol. 14 Issue 3 Pg. 351-9 (Sep 2008) ISSN: 1738-222X [Print] Korea (South)
• PMID: 18815458 (Publication Type: Journal Article)

Chemical References

• BIRC5 protein, human
• Cyclooxygenase 2 Inhibitors
• Inhibitor of Apoptosis Proteins
• Microtubule-Associated Proteins
• Neoplasm Proteins
• Nitrobenzenes
• Sulfonamides
• Survivin
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide

Topics

• Carcinoma, Hepatocellular (enzymology, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclooxygenase 2 Inhibitors (chemistry, pharmacology)
• G1 Phase
• Humans
• Inhibitor of Apoptosis Proteins
• 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)
• Survivin
• Time Factors