Effects of various prostaglandin synthesis inhibitors on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine

Abstract

The effects of prostaglandin synthesis inhibitors on development of N-nitrosobis(2-oxopropyl)amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given five weekly s.c. injections of BOP (10 mg/kg body weight) during the first 5 weeks and then given 20 p.p.m. indomethacin in the drinking water, 0.25% phenylbutazone in the diet, 1% aspirin in the diet, or no treatment (control group). The resultant incidence of pancreatic carcinoma at week 32 was significantly lower (P less than 0.05) in animals receiving phenylbutazone (36.8%) than in the controls (71.4%) and the numbers of carcinomas per hamster were significantly reduced by indomethacin (0.63) and phenylbutazone (0.58) treatment compared with the control group value (1.29). Aspirin also showed a tendency to decrease pancreatic tumor incidence, but this was not significant. Thus, prostaglandin synthesis inhibitors reduce the development of pancreatic cancer when administered during the post-initiation phase in this animal model.

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

“…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. Previously, we also reported that NSAIDs such as indomethacin and phenylbutazone can reduce the development of pancreatic cancer when administered during the postinitiation phase in the hamster N-nitrosobis(2-oxopropyl)amine (BOP) model, 23 strongly supporting the present study with nimesulide.…”

“…To detect pancreatic proliferative lesions, 4 parts of the pancreas (splenic, duodenal and gastric lobes and head portion) were serially sectioned according to our routine method. 23,[25][26][27] Neoplastic and preneoplastic lesions were histopathologically diagnosed as adenocarcinomas and atypical hyperplasias and counted in representative sections, as usually performed in our laboratory. 23,[25][26][27] For COX-2 immunohistochemistry, the primary COX-2 polyclonal antibody (Cayman Chemical, Ann Arbor, MI) was used at a 1:100 dilution together with the Vectastain Elite ABC kit (Vector, Burlingame, CA) according to the modified method previously reported.…”

Celecoxib inhibits angiogenesis by inducing endothelial cell apoptosis in human pancreatic tumor xenografts

“…[6][7][8] With regards to pancreatic cancer, COX-2 is overexpressed in human pancreatic neoplasms, suggesting that it may play a role in tumor progression. [9][10][11][12] Furthermore, prostaglandin synthesis antagonists (NSAIDs) inhibited the development of tumors in a hamster model of chemically-induced pancreatic cancer, 13 and epidemiological data suggest that aspirin dramatically decreases the risk of developing pancreatic cancer. 14 Although accumulating evidence implicates COX-2 in tumor progression, its mechanisms of action remain poorly characterized and controversial.…”

Chemoprevention of gastrointestinal malignancies with nonsteroidal antiinflammatory drugs

“…Takahashi et al 50 treated hamsters with this agent and then subsequently treated them with indomethacin, phenylbutazone, or aspirin. Animals in the indomethacin and phenylbutazone groups displayed fewer tumors than the control group.…”