在F344大鼠中，通过给予牛乳铁蛋白抑制偶氮甲烷引发的结肠肿瘤和异常隐窝病灶发展。

Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats.

作者信息

Tsuda H, Sekine K, Nakamura J, Ushida Y, Kuhara T, Takasuka N, Kim D J, Asamoto M, Baba-Toriyama H, Moore M A, Nishino H, Kakizoe T

机构信息

Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.

出版信息

Adv Exp Med Biol. 1998;443:273-84. doi: 10.1007/978-1-4757-9068-9_34.

DOI:10.1007/978-1-4757-9068-9_34

PMID:9781370

Abstract

The influence of bovine lactoferrin (bLf) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). In experiment I, 2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at 3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by both treatments. Similar results were obtained in experiment II of 13 weeks duration. In experiment III, animals were given three weekly injections of AOM and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin (bLfcin) for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with almost all the treatments. Thus, the incidences of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced development. Investigation of beta-glucuronidase revealed decrease in the cecal contents of animals receiving bLf. In addition, demonstration of enhancement of NK activity by bLf indicated that its inhibitory effects could have been related to elevated immune cytotoxicity.

摘要

在接受偶氮甲烷（AOM）处理的雄性F344大鼠中，研究了牛乳铁蛋白（bLf）对结肠癌发生的影响。在实验I中，将2%和0.2%的bLf以及作为阳性对照的3%的长双歧杆菌（B. longum）添加到饮食中4周，同时在第1天和第8天皮下注射两次15 mg/kg的AOM。两种处理均使异常隐窝病灶（ACF）数量减少。在为期13周的实验II中也获得了类似结果。在实验III中，动物每周注射三次AOM，然后接受2%或0.2%的bLf、2%的bLf水解产物或0.1%的牛乳铁蛋白素（bLfcin），持续36周。未观察到毒性迹象，但几乎所有处理均使大肠腺癌的发生率和数量显著降低。因此，接受2%或0.2%的bLf、2%的bLf水解产物或0.1%的bLfcin的组中，结肠腺癌的发生率分别为15%、25%、26.3%和仅10%，而对照组为57.5%（p < 0.01）。ACF值也显示出发育减少。对β-葡萄糖醛酸酶的研究表明，接受bLf的动物盲肠内容物减少。此外，bLf增强NK活性的证明表明其抑制作用可能与免疫细胞毒性升高有关。