PMID- 16419156
OWN - NLM
STAT- MEDLINE
DCOM- 20060302
LR  - 20190430
IS  - 1007-9327 (Print)
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Linking)
VI  - 11
IP  - 40
DP  - 2005 Oct 28
TI  - Overexpression of cyclooxygenase-2 in human HepG2, Bel-7402 and SMMC-7721 
      hepatoma cell lines and mechanism of cyclooxygenase-2 selective inhibitor 
      celecoxib-induced cell growth inhibition and apoptosis.
PG  - 6281-7
AB  - AIM: To investigate the cyclooxygenase-2 (COX-2) expression level in human HepG2, 
      Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 
      selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis. 
      METHODS: Hepatoma cells were cultured and treated with celecoxib. Cell in situ 
      hybridization (ISH) and immunocytochemistry were used to detect COX-2 mRNA and 
      protein expression. Proliferating cell nuclear antigen and phosphorylated Akt 
      were also detected by immunocytochemistry assay. Cell growth rates were assessed 
      by 3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium (MTT) bromide 
      colorimetric assay. Celecoxib-induced cell apoptosis was measured by terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and flow 
      cytometry (FCM). The phosphorylated Akt and activated fragments of caspase-9, 
      caspase-3 were examined by Western blotting analysis. RESULTS: Increased COX-2 
      mRNA and protein expression were detected in all three hepatoma cell lines. 
      Celecoxib could significantly inhibit cell growth and the inhibitory effect was 
      in a dose- and time-dependent manner evidenced by MTT assays and morphological 
      changes. The apoptotic index measured by TUNEL increased correspondingly with the 
      increased concentration of celecoxib and the reaction time. With 50 micromol/L 
      celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and 
      SMMC-7721 cells was 25.01+/-3.08%, 26.40+/-3.05%, and 30.60+/-2.89%, 
      respectively. Western blotting analysis showed remarkable activation of 
      caspase-9, caspase-3 and dephosphorylation of Akt (Thr(308)). Immunocytochemistry 
      also showed the reduction of PCNA expression and phosphorylation Akt (Thr(308)) 
      after treatment with celecoxib. CONCLUSION: COX-2 mRNA and protein overexpression 
      in HepG2, Bel-7402 and SMMC-7721 cell lines correlate with the increased cell 
      growth rate. Celecoxib can inhibit proliferation and induce apoptosis of hepatoma 
      cell strains in a dose- and time-dependent manner.
FAU - Liu, Ning-Bo
AU  - Liu NB
AD  - Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical 
      University, Nanjing 210029, Jiangsu Province, China.
FAU - Peng, Tao
AU  - Peng T
FAU - Pan, Chao
AU  - Pan C
FAU - Yao, Yu-Yu
AU  - Yao YY
FAU - Shen, Bo
AU  - Shen B
FAU - Leng, Jing
AU  - Leng J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
RN  - JCX84Q7J1L (Celecoxib)
SB  - IM
MH  - Apoptosis/*drug effects/physiology
MH  - *Carcinoma, Hepatocellular
MH  - Caspase 3
MH  - Caspase 9
MH  - Caspases/metabolism
MH  - Celecoxib
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Cyclooxygenase 2 Inhibitors/*pharmacology
MH  - Enzyme Activation
MH  - Humans
MH  - In Situ Hybridization
MH  - *Liver Neoplasms
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyrazoles/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Sulfonamides/*pharmacology
PMC - PMC4320331
EDAT- 2006/01/19 09:00
MHDA- 2006/03/03 09:00
PMCR- 2005/10/28
CRDT- 2006/01/19 09:00
PHST- 2006/01/19 09:00 [pubmed]
PHST- 2006/03/03 09:00 [medline]
PHST- 2006/01/19 09:00 [entrez]
PHST- 2005/10/28 00:00 [pmc-release]
AID - 10.3748/wjg.v11.i40.6281 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2005 Oct 28;11(40):6281-7. doi: 10.3748/wjg.v11.i40.6281.