Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor.
10.3350/kjhep.2008.14.3.351
- Author:
Il Han SONG
1
;
Dong Woo KIM
;
Ki Chul SHIN
;
Hyun Duk SHIN
;
Se Young YUN
;
Suk Bae KIM
;
Jung Eun SHIN
;
Hong Ja KIM
;
Eun Young KIM
Author Information
1. Department of Internal Medicine, Dankook University College of Medicine, Dankook University Hospital Institute of Medical Science, Cheonan, Korea. ihsong21@dankook.ac.kr
- Publication Type:Original Article ; English Abstract
- Keywords:
Carcinoma, hepatocellular;
Survivin;
Cyclooxygenase-2 (COX-2);
COX-2 inhibitor, Apoptosis
- MeSH:
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
- From:The Korean Journal of Hepatology
2008;14(3):351-359
- CountryRepublic of Korea
- Language:Korean
-
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.
