title: [Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective cyclooxygenase-2 inhibitor].
abstract: 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.
authors.affiliation: Department of Internal Medicine, Dankook University College of Medicine, Dankook University Hospital Institute of Medical Science, Cheonan, Korea. ihsong21@dankook.ac.kr
authors.forename: Il Han
authors.initials: IH
authors.lastname: Song
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Kim
authors.forename: Ki Chul
authors.initials: KC
authors.lastname: Shin
authors.forename: Hyun Duk
authors.initials: HD
authors.lastname: Shin
authors.forename: Se Young
authors.initials: SY
authors.lastname: Yun
authors.forename: Suk Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Shin
authors.forename: Hong Ja
authors.initials: HJ
authors.lastname: Kim
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
mesh_terms: 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
chemical_list: 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