Review
Copyright ©2006 Baishideng Publishing Group Co.
World J Gastroenterol. Mar 7, 2006; 12(9): 1336-1345
Published online Mar 7, 2006. doi: 10.3748/wjg.v12.i9.1336
Table 1 Selective COX-2 inhibitors (coxibs) and chemoprevention in gastrointestinal tract tumors
Generic nameBrand namePhCobEsophagus
Stomach
Colorectum
Cancer cell lineCIAcreflux-induced animalHuman (BEd)Cancer cell lineCIAcMIAeCancer cell lineCIAcMIAeHuman (FAPf)
Tricyclic
CelecoxibCelebrexPfizer(23)(46,47)(75)(76,77)(81,82)(54)(56)
MF-tricyclicECaMerck(21)(53,87)
RofecoxibVioxxMerck(24)(55)
TilmacoxibJapan Tobacco(20)(78)(88,89)
Valdecoxib BextraPfizer
EtoricoxibArcoxiaMerck
Methanesulphonamide
NS-398ECaTaisho(18,19,70,71)(44,45,72)(49)(72)(83)
NimesulideMesulidHelsinn(73)(48)(84)(90)
FlosulideSchering(70)
Others
NabumetoneRelafenGlaxo Smith Kline(85)(91)
MeloxicamMobicBoehringer Ingelheim(79,80)(86)
EtodolacLodineWyeth(74)(74)
LumiracoxibPrexigeNovartis
Table 2 Incidences of inflammatory changes, Barrett’s esophagus, and adenocarcinoma in a rodent duodenoesophageal reflux model
WkGroupnRT#BCH$Incidence (%) of
Barrett's esophagusAdeno- carcinom
10Control10100c100c100
Celecoxib5404000
20Control10100c100c400
Celecoxib54040200
30Control10100c100c5010
Celecoxib54040400
40Control19100c100c89a47b
Celecoxib83838250
Table 3 Chemopreventive effects of coxibs on intestinal tumors using animal models
DrugOutcomesReference
Name
Concentration
Term
Animal model
Inhibition rate (%)
P value
Reporter (#)
Year
carcinogen-induced rat model
Celecoxib1500 ppm5-16 wkF344 rat, AOMa40 (ACF)P < 0.001Reddy et al (92)1996
NS-3981 mg/kg•bw5-11 wkF344 rat, AOMa34 (ACF)P < 0.05Yoshimi et al (83)1997
10 mg/kg•bw47 (ACF)P < 0.01
Celecoxib1500 ppm5-50 wkF344rat, AOMa93(colontumor)P<0.00001Kawamori et al (81)1998
Nimesulide200 ppm6-30 wkICRmouse,AOMa36(adenocarcinoma)NSFukutake et al (84)1998
400 ppm50(adenocarcinoma)P < 0.05
Celecoxib500 ppm5-58 wkF344 rat, AOMa55(adenocarcinoma)P < 0.001Reddyet al (82)2000
1000 ppm5-58 wk62(adenocarcinoma)P < 0.001
1500 ppm5-58 wk77(adenocarcinoma)P < 0.0001
1500 ppm22-58 wk47(adenocarcinoma)P < 0.01
Nabumetone750 ppmfor18 wkF344 rat, AOMa15 (ACF)P < 0.05Roy et al (85)2001
1500 ppm37 (ACF)P < 0.01
Apc gene mutant mouse model
MF-tricyclic3,5 mg/kg•d3-11 wkApcΔ71652(intestinalpolyp)P = 0.0037Oshima et al (53)1996
14 mg/kg•d62 (intestinal polyp)P < 0.0001
Nimesulide400 ppm4-15 wkApcΔ850 (Min)48 (intestinal polyp)Nakatsugi et al (90)1997
Celecoxib150 ppm30-80 dApcΔ850 (Min)48 (intestinal polyp)P < 0.05Jacoby et al (54)2000
500 ppm29(intestinalpolyp)
1500 ppm71(intestinalpolyp)
JTE-5220.001 (%)4-12 wkApcΔ4749 (intestinal polyp)NSSasai et al (88)2000
0.01 (%)32 (intestinal polyp)P < 0.05
Nabumetone900 ppm5-15 wkApcΔ850 (Min)50(smallbowelpolyp)P < 0.05Roy et al (91)2001
65(largebowelpolyp)P < 0.05
MF-tricyclic13 mg/kg/d3-7 wkApcΔ850 (Min) +48 (intestinal polyp)P < 0.001Lal et al (87)2001
Msh2-/-
Rofecoxib0.0025 (%)3-11 wkApcΔ71636 (intestinal polyp)Oshima et al (55)2001
0.0075 (%)55 (intestinal polyp)
JTE-5220.01 (%)4-12 wkApcΔ47449 (large adenoma)P < 0.01Sunayama et al (89)2001
-28 (small adenoma)NS