PMID- 12800245
OWN - NLM
STAT- MEDLINE
DCOM- 20030912
LR  - 20220318
IS  - 1007-9327 (Print)
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Linking)
VI  - 9
IP  - 6
DP  - 2003 Jun
TI  - Celecoxib inhibits proliferation and induces apoptosis via prostaglandin E2 
      pathway in human cholangiocarcinoma cell lines.
PG  - 1302-6
AB  - AIM: To evaluate the roles and mechanisms of celecoxib in inducing proliferation 
      inhibition and apoptosis of human cholangiocarcinoma cell lines. METHODS: 
      Cyclooxygenase-2-overexpressing human cholangiocarcinoma cell line QBC939 and 
      cyclooxygenase-2-deficient human cholangiocarcinoma cell line SK-CHA-1 were used 
      in the present study. The anti-proliferative effect was measured by 
      methabenzthiazuron (MTT) assay; apoptosis was determined by transferase-mediated 
      dUTP nick end labeling (TUNEL) detection and transmission electron microscopy 
      (TEM). Cell cycle was analyzed by flow cytometry (FCM). The PGE(2) levels in the 
      supernatant of cultured cholangiocarcinoma cells were quantitated by 
      enzyme-linked immunoabsordent assay (ELISA). RESULTS: Celecoxib suppressed the 
      production of PGE(2) and inhibited the growth of QBC939 cells. Celecoxib at 10, 
      20, and 40 micromol/L inhibited PGE(2) production by 26 %, 58 %, and 74 % in 
      QBC939 cells. The PGE(2) level was much lower constitutively in SK-CHA-1 cells 
      (18.6+/-3.2) compared with that in QBC939 (121.9+/-5.6) cells (P<0.01) and 
      celecoxib had no significant influence on PGE(2) level in the SK-CHA-1 cells. The 
      PGE(2) concentration in SK-CHA-1 cells also reduced but not significantly after 
      treatment with celecoxib. The PGE(2) concentration in SK-CHA-1 cells was 
      (16.5+/-2.9) ng/well, (14.8+/-3.4) ng/well, (13.2+/-2.0) ng/well and (12.6+/-3.1) 
      ng/well respectively, when pre-treated with 1 micromol/L, 10 micromol/L, 20 
      micromol/L and 40 micromol/L of celecoxib for 48 h (P>0.05, vs control). The 
      anti-proliferation effect of celecoxib (20 micromol/L) on QBC939 cells was 
      time-dependent, it was noticeable on day 2 (OD490=0.23+/-0.04) and became obvious 
      on day 3 (OD490=0.31+/-0.07) to day 4 (OD490= 0.25+/-0.06), and the OD490 in the 
      control group (day 1) was 0.12+/-0.03 (P<0.01, vs control). The 
      anti-proliferation effect of celecoxib could be abolished by the addition of 200 
      pg/mL PGE(2). The proliferation of SK-CHA-1 cells was inhibited slightly by 
      celecoxib, the cell density OD490 in the presence of celecoxib and in control 
      group was 0.31+/-0.04 and 0.42+/-0.03 respectively on day 2 (P>0.05), 0.58+/-0.07 
      and 0.67+/-0.09 respectively on day 3 (P>0.05), and 0.71+/-0.08 and 0.78+/-0.06 
      respectively on day 4 (P>0.05). Celecoxib induced proliferation inhibition and 
      apoptosis by G(1)-S cell cycle arrest: the percentage of QBC939 cells in 
      G(0)-G(1) phase after treatment with 40 micromol/L (74.66+/-6.21) and 20 
      micromol/L (68.63+/-4.36) celecoxib increased significantly compared with control 
      cells (54.41+/-5.12, P<0.01). The percentage of SK-CHA-1 cells in G(0)-G(1) phase 
      after treatment with various concentrations of celecoxib didn't change 
      significantly compared with control cells. The TUNEL index was much higher in 
      QBC939 cells treated with 20 micromol/L celecoxib for 2 d (0.063+/-0.018) and for 
      4 d (0.102+/-0.037) compared with control cells (0.017+/-0.004, P<0.01). 
      CONCLUSION: The current in vitro study indicates that inhibition of proliferation 
      and induction of apoptosis in human cholangiocarcinoma cells by cyclooxygenase-2 
      specific inhibitor celecoxib may involve in COX-dependent mechanisms and PGE(2) 
      pathway. Celecoxib as a chemopreventive and chemotherapeutic agent might be 
      effective primarily on COX-2-expressing cholangiocarcinoma.
FAU - Wu, Gao-Song
AU  - Wu GS
AD  - Department of General Surgery, Tongji Hospital, 1095 Jiefang Road, Wuhan, 430030, 
      Hubei Province, China. wugaosong9172@sina.com
FAU - Zou, Sheng-Quan
AU  - Zou SQ
FAU - Liu, Zheng-Ren
AU  - Liu ZR
FAU - Tang, Zhao-Hui
AU  - Tang ZH
FAU - Wang, Ju-Hua
AU  - Wang JH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Proteins)
RN  - 0 (Pyrazoles)
RN  - 0 (Sulfonamides)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - JCX84Q7J1L (Celecoxib)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis
MH  - Bile Duct Neoplasms/*pathology/*physiopathology
MH  - *Bile Ducts, Intrahepatic
MH  - Celecoxib
MH  - Cell Division/drug effects
MH  - Cholangiocarcinoma/*pathology/*physiopathology
MH  - Cyclooxygenase 2
MH  - Cyclooxygenase 2 Inhibitors
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - Dinoprostone/metabolism
MH  - Humans
MH  - Isoenzymes/antagonists & inhibitors
MH  - Membrane Proteins
MH  - Prostaglandin-Endoperoxide Synthases
MH  - Pyrazoles
MH  - Sulfonamides/*pharmacology
MH  - Tumor Cells, Cultured/drug effects
PMC - PMC4611805
EDAT- 2003/06/12 05:00
MHDA- 2003/09/13 05:00
PMCR- 2003/06/15
CRDT- 2003/06/12 05:00
PHST- 2003/06/12 05:00 [pubmed]
PHST- 2003/09/13 05:00 [medline]
PHST- 2003/06/12 05:00 [entrez]
PHST- 2003/06/15 00:00 [pmc-release]
AID - 10.3748/wjg.v9.i6.1302 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2003 Jun;9(6):1302-6. doi: 10.3748/wjg.v9.i6.1302.