| Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor |
| Il Han Song, M.D., Dong Woo Kim, M.D., Ki Chul Shin, M.D.,
Hyun Duk Shin, M.D., Se Young Yun, M.D., Suk Bae Kim, M.D.,
Jung Eun Shin, M.D., Hong Ja Kim, M.D., Eun Young Kim, M.D. |
| Department of Internal Medicine, Dankook University College of Medicine, Dankook University Hospital Institute of Medical Science, Cheonan, Korea |
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| ABSTRACT |
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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) |
| KeyWords:
Carcinoma, hepatocellular; Survivin; Cyclooxygenase-2 (COX-2); COX-2 inhibitor, Apoptosis |
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