Suppressive effects of nimesulide, a selective inhibitor of cyclooxygenase-2, on azoxymethane-induced colon carcinogenesis in mice

Fukutake, Masato

doi:10.1093/carcin/19.11.1939

Cited by 108 publications

(67 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that nimesulide, a cyclooxygenase-2 selective inhibitor, showed a remarkable suppressive effect on rodent carcinogenesis but the mechanisms were not identified (5).…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma cruzi infection and/or administration of the nonsteroidal anti-inflammatory nimesulide increase the number of colonic crypts overexpressing metallothioneins in rat colon carcinogenesis

Escalante

Oliveira

Cunha

et al. 2006

Braz J Med Biol Res

View full text Add to dashboard Cite

Trypanosoma cruzi infection and nonsteroidal anti-inflammatory drugs inhibit colorectal carcinogenesis by mechanisms not completely known and metallothionein proteins (MTs) may be involved in this process. Sixty-six male Wistar rats weighing 90 to 120 g were randomly divided into seven groups (GI to GVII). GI, GII and GIII animals were subcutaneously infected with 200,000 trypomastigote forms of the Y strain of T. cruzi. After 8 weeks, GI, GII, GIV, and GVI were injected with one weekly subcutaneous dose of 12 mg/kg dimethylhydrazine for 4 weeks. In sequence, GI, GIV and GV were treated with nimesulide (10 mg/kg per dose, five times per week for 8 weeks). Groups I, III, IV, and VI had 12 animals, and each of the other groups had 6 animals. All the animals were euthanized 8 weeks after the last dimethylhydrazine injection. The colons were fixed and processed for MT immunohistochemistry. The index of MT-overexpressing colonic crypts (MTEC) was estimated as the percentage of MT-stained crypts in relation to the total number of crypts scored. Five hundred crypts per animal were scored. Data were analyzed by the Kruskal-Wallis test followed by the Dunn test. There was an increase in MTEC index in the groups either infected with T. cruzi or treated with nimesulide or both infected and treated when compared to control (401, 809, and 1011%, respectively). We suggest that the increased formation of MTEC may be related to the protection against carcinogenesis provided both by T. cruzi infection and nimesulide.

show abstract

“…It has been reported that nimesulide, a cyclooxygenase-2 selective inhibitor, showed a remarkable suppressive effect on rodent carcinogenesis but the mechanisms were not identified (5).…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma cruzi infection and/or administration of the nonsteroidal anti-inflammatory nimesulide increase the number of colonic crypts overexpressing metallothioneins in rat colon carcinogenesis

Escalante

Oliveira

Cunha

et al. 2006

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…This supporting evidence includes the observation that COX isoenzymes are overexpressed in colorectal adenomas and tumors (74 -82). Targeted deletion of the COX-2 gene prevents CRC in animals, and celecoxib as well as other selective COX-2 inhibitors (e.g., JTE-522, NS-398, the tricyclic methyl sulfone derivative MF tricyclic, nimesulide, and rofecoxib) are also effective in preclinical models (83)(84)(85)(86)(87)(88)(89)(90)(91) The Subpart H approval was based on a randomized, double-blind, placebo-controlled study of 83 FAP patients in which 400 mg twice daily celecoxib for 6 months significantly reduced adenoma number by 28% [P ϭ 0.003 compared with the 4.5% reduction with placebo (100)]. In addition, this celecoxib dose significantly reduced adenoma burden (the sum of adenoma diameters) by 30.7% (P ϭ 0.001 compared with the 4.9% reduction with placebo).…”

Section: Celecoxib Celecoxib Has a Known Molecular Target [Cyclooxygmentioning

confidence: 99%

Colorectal Adenomas

Kelloff

Schilsky

Alberts

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

“…Doses were selected on the basis of previous experimental results for mice or rats. 19,20,22 Groups 4 and 5, consisting of 10 animals each, were fed a diet supplemented with nimesulide 400 or 0 ppm, respectively, without prior initiation. Hamsters were observed daily and weighed once every 4 weeks.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…4 It is now clear that COX-2 is an inducible immediate early gene, 11 involved not only in inflammation and cell proliferation 11 but also in differentiation, 12 apoptosis, 13 metastasis, 14 immunologic surveillance 15 and angiogenesis. 16 Nimesulide, a preferential COX-2 inhibitor of nonsteroidal antiinflammatory drugs (NSAIDs), 17 inhibits chemically induced colon, 18,19 mammary, 20 tongue 21 and urinary bladder 22 carcinogenesis in rats. However, it is still important to examine the modifying effects of nimesulide on pancreatic carcinogenesis because the postinitiation and promotion stages are supposed to be organspecific.…”

mentioning

confidence: 99%

A cyclooxygenase‐2 inhibitor, nimesulide, inhibits postinitiation phase of N‐nitrosobis(2‐oxopropyl)amine‐induced pancreatic carcinogenesis in hamsters

Furukawa

Nishikawa

Lee

et al. 2003

Intl Journal of Cancer

View full text Add to dashboard Cite

The modification effects of nimesulide, a cyclooxygenase (COX)-2 inhibitor, administration during the postinitiation phase of pancreatic carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Male Syrian hamsters were given 4 weekly s.c. injections of BOP at a dose of 10 mg/kg and thereafter administered 0, 100 or 400 ppm nimesulide in the diet for 36 weeks. Additional groups of hamsters were fed 400 ppm nimesulide without prior BOP initiation or nontreated. At week 40, all surviving animals were killed and development of neoplastic and preneoplastic lesions was assessed histopathologically. The incidence of pancreatic adenocarcinomas was significantly (p < 0.05) decreased in the BOP/400 ppm nimesulide group compared to the BOP alone group. The multiplicity of total lesions of pancreatic adenocarcinoma plus atypical hyperplasia was also significantly (p < 0.05) lowered. Immunohistochemically, COX-2 was clearly expressed in pancreatic and lung tumor cells, whereas expression was not remarkably affected by the 400 ppm nimesulide treatment. Proliferating cell nuclear antigen labeling indices of pancreatic ducts were significantly (p < 0.01) reduced by nimesulide. The incidence and multiplicity of neoplastic lesions in other organs did not significantly differ among the BOP-treated groups, though only the multiplicity of lung tumors showed a tendency to decrease. No neoplastic lesions were detected in animals receiving nimesulide alone. Our results clearly indicate that nimesulide protects against BOP-induced pancreatic tumors in hamsters.

show abstract

Suppressive effects of nimesulide, a selective inhibitor of cyclooxygenase-2, on azoxymethane-induced colon carcinogenesis in mice

Abstract: The effects of nimesulide, a selective inhibitor of cyclooxygenase-2 (COX-2) on azoxymethane (AOM)-induced colon carcinogenesis were investigated in mice. AOM at a dose of 10 mg/kg body wt was administered to male ICR mice once a week for 6 weeks.

Cited by 108 publications

References 22 publications

Trypanosoma cruzi infection and/or administration of the nonsteroidal anti-inflammatory nimesulide increase the number of colonic crypts overexpressing metallothioneins in rat colon carcinogenesis

Trypanosoma cruzi infection and/or administration of the nonsteroidal anti-inflammatory nimesulide increase the number of colonic crypts overexpressing metallothioneins in rat colon carcinogenesis

Colorectal Adenomas

A cyclooxygenase‐2 inhibitor, nimesulide, inhibits postinitiation phase of N‐nitrosobis(2‐oxopropyl)amine‐induced pancreatic carcinogenesis in hamsters

Contact Info

Product

Resources

About