Chemopreventive Properties of Black Raspberries in N-Nitrosomethylbenzylamine-Induced Rat Esophageal Tumorigenesis: Down-regulation of Cyclooxygenase-2, Inducible Nitric Oxide Synthase, and c-Jun
kane35 添加于 2010-8-7 10:43
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作 者
Chen T
摘 要
Our laboratory has used a rodent model of human esophageal
squamous cell carcinoma to identify putative chemopreventive
agents for this disease and to determine their mechanisms
of action. In the present study, we treated F344 rats with the
esophageal carcinogen, N-nitrosomethylbenzylamine (NMBA),
thrice per week for 5 weeks. Beginning 1 week later, they were
fed a synthetic diet containing 5% black raspberries (BRB) for
the duration of the bioassay (25 weeks). Rats were sacrificed
at weeks 9, 15, and 25. Esophageal tissues were collected,
and tumor data were recorded. The expression and enzymatic
activities of cyclooxygenase-2 (COX-2) and inducible nitric
oxide synthase (iNOS) as well as the expression of c-Jun in the
esophagi, were evaluated to investigate the mechanism(s) by
which black raspberries modulate tumorigenesis. At week 25,
BRB inhibited tumor multiplicity, the standard end point in
this tumor model, from 3.78 F 0.41 tumors per rat in NMBAtreated
animals to 2.23 F 0.21 tumors per rat in animals
treated with NMBA plus BRB (P < 0.005). BRB reduced mRNA
and protein expression levels of COX-2, iNOS, and c-Jun as well
as the level of prostaglandin E2 in preneoplastic lesions of the
esophagus at week 25. The berries inhibited mRNA expression
of iNOS and c-Jun, but not COX-2, in papillomatous lesions of
the esophagus. Prostaglandin E2 and total nitrite levels were
also decreased by BRB in papillomas. These results suggest
a novel tumor suppressive role of BRB through inhibition of
COX-2, iNOS, and c-Jun. -
详细资料
- 文献种类:期刊
- 期刊名称: Cancer Research
- 期刊缩写: Cancer Research
- 期卷页: 2006年 第66卷 第5期 2853-2859页
- ISBN: 0008-5472
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