Singh J, Rivenson A, Tomita M, Shimamura S, Ishibashi N, Reddy B S
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, NY 10595, USA.
Carcinogenesis. 1997 Apr;18(4):833-41. doi: 10.1093/carcin/18.4.833.
The human colon can be described as a complex microbial ecosystem, comprising several hundred bacterial species. Some of these enteric bacteria are beneficial to the host and have been shown to exert antimutagenic and anticarcinogenic properties. We have investigated the colon tumor inhibitory activity of Bifidobacterium longum, a lactic acid-producing enterobacterium. The modifying effects of this lactic culture on colonic mucosal and/or tumor cell proliferation, ODC activity and ras-p21 oncoprotein expression in colon carcinogenesis were also analyzed. Male F344 rats were fed a modified AIN-76A diet containing 0 or 2% lyophilized cultures of B. longum and s.c. administered azoxymethane (AOM) dissolved in normal saline at a dose of 15 mg/kg body wt, once weekly for 2 weeks. Vehicle controls received an equal volume of normal saline s.c. Animals were maintained on control or experimental diets until termination of the study. Animals intended for analysis of cell proliferation were killed 20 weeks after the second AOM injection, whereas animals intended for colon tumor analysis and measurement of ODC activity and ras-p21 expression were killed 40 weeks after the last AOM injection. The data demonstrate that dietary administration of lyophilized cultures of B. longum resulted in significant suppression of colon tumor incidence and tumor multiplicity and also reduced tumor volume. Results also revealed that ingestion of B. longum significantly inhibited AOM-induced cell proliferation, ODC activity and expression of ras-p21 oncoprotein. Data suggest that oral administration of probiotic B. longum exerts strong antitumor activity, as indicated by modulation of the intermediate biomarkers of colon cancer, and consequently reduced tumor outcome.
人类结肠可被描述为一个复杂的微生物生态系统,由数百种细菌组成。其中一些肠道细菌对宿主有益,并已显示出具有抗诱变和抗癌特性。我们研究了长双歧杆菌(一种产乳酸的肠道细菌)对结肠肿瘤的抑制活性。还分析了这种乳酸培养物对结肠癌发生过程中结肠黏膜和/或肿瘤细胞增殖、鸟氨酸脱羧酶(ODC)活性以及ras-p21癌蛋白表达的调节作用。给雄性F344大鼠喂食含有0%或2%长双歧杆菌冻干培养物的改良AIN-76A饮食,并皮下注射溶解于生理盐水中、剂量为15mg/kg体重的氧化偶氮甲烷(AOM),每周一次,共2周。溶剂对照组皮下注射等量的生理盐水。动物维持对照或实验饮食直至研究结束。用于分析细胞增殖的动物在第二次注射AOM后20周处死,而用于结肠肿瘤分析以及ODC活性和ras-p21表达测定的动物在最后一次注射AOM后40周处死。数据表明,饮食中给予长双歧杆菌冻干培养物可显著抑制结肠肿瘤的发生率和肿瘤多发性,还可减小肿瘤体积。结果还显示,摄入长双歧杆菌可显著抑制AOM诱导的细胞增殖、ODC活性以及ras-p21癌蛋白的表达。数据表明,口服益生菌长双歧杆菌具有强大的抗肿瘤活性,如通过调节结肠癌的中间生物标志物所示,从而降低了肿瘤发生结果。