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鼠 Apc(Min)模型(一种结直肠肿瘤发生模型)对迷迭香酸的膳食摄入量:靶组织中母体药物的水平及其对腺瘤发生的影响。

Dietary intake of rosmarinic acid by Apc(Min) mice, a model of colorectal carcinogenesis: levels of parent agent in the target tissue and effect on adenoma development.

机构信息

Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.

出版信息

Mol Nutr Food Res. 2012 May;56(5):775-83. doi: 10.1002/mnfr.201100617.

DOI:10.1002/mnfr.201100617
PMID:22648624
Abstract

SCOPE

Rosmarinic acid (RA), a constituent of culinary herbs is considered to possess cancer chemopreventive properties. It has been shown to inhibit the development of cancer in preclinical models but data are conflicting and whether it can protect against gastrointestinal malignancies in vivo has not been examined. This study aimed to investigate the effect of RA on the development of intestinal adenomas in the Apc(Min) mouse model of colorectal carcinogenesis, and to correlate efficacy with levels of RA achieved in the plasma and gastrointestinal tract.

METHODS AND RESULTS

RA inhibited the growth of APC10.1 cells derived from Apc(Min) mouse adenomas, with an IC₅₀ of 43 μM. Consumption of dietary RA (0.3%) by Apc(Min) mice for 8 weeks post weaning decreased adenoma burden by ∼35%, but the difference from controls was not significant. Although RA significantly decreased the frequency of large adenomas, the number of small ones increased. Using a novel validated HPLC assay, average levels of RA in the plasma and intestinal mucosa of these mice were found to be 1.1 μM and 38 nmol/g, respectively.

CONCLUSION

Chronic consumption of RA furnished quantifiable levels of parent compound in the plasma and intestinal tract of Apc(Min) mice and may slow adenoma development.

摘要

范围

迷迭香酸(RA)是烹饪香草的一种成分,被认为具有抗癌化学预防特性。已表明它可以抑制临床前模型中癌症的发展,但数据相互矛盾,并且它是否可以防止体内胃肠道恶性肿瘤尚未得到检验。本研究旨在研究 RA 对大肠癌发生的 Apc(Min)小鼠模型中肠腺瘤发展的影响,并将疗效与血浆和胃肠道中达到的 RA 水平相关联。

方法和结果

RA 抑制了源自 Apc(Min)小鼠腺瘤的 APC10.1 细胞的生长,IC₅₀为 43 μM。断奶后 8 周,Apc(Min)小鼠通过饮食摄入 RA(0.3%)可使腺瘤负担减少约 35%,但与对照组相比差异无统计学意义。尽管 RA 显著降低了大腺瘤的频率,但小腺瘤的数量却增加了。使用一种新的经过验证的 HPLC 测定法,发现这些小鼠的血浆和肠黏膜中的 RA 平均水平分别为 1.1 μM 和 38 nmol/g。

结论

慢性消耗 RA 可在 Apc(Min)小鼠的血浆和肠道中提供可量化的母体化合物水平,并可能减缓腺瘤的发展。

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EXCLI J. 2014 Oct 30;13:1192-5. eCollection 2014.