Femia Angelo Pietro, Luceri Cristina, Dolara Piero, Giannini Augusto, Biggeri Annibale, Salvadori Maddalena, Clune Yvonne, Collins Kevin J, Paglierani Milena, Caderni Giovanna
Department of Pharmacology, University of Florence, 6 Viale Pieraccini, 50139 Florence, Italy.
Carcinogenesis. 2002 Nov;23(11):1953-60. doi: 10.1093/carcin/23.11.1953.
Prebiotics such as fructans, and probiotics such as Lactobacilli or Bifidobacteria, or a combination of prebiotics and probiotics (synbiotics) are thought to be protective against colon cancer. Therefore, we studied whether the prebiotic inulin enriched with oligofructose (Raftilose-Synergy1, briefly, Synergy1, 10% of the diet), probiotics [Bifidobacterium lactis (Bb12) and Lactobacillus rhamnosus (LGG), each at 5x10(8) c.f.u./g diet] or synbiotics (a combination of the two) protect rats against azoxymethane (AOM)-induced colon cancer. Male F344 rats were divided into: Controls; PRE, which were fed a diet containing Synergy1; PRO, fed a diet containing LGG and Bb12; PREPRO, fed a diet containing Synergy1, LGG and BB12. Ten days after beginning the diets, rats were treated with AOM (15 mg/kg s.c. two times); dietary treatments were continued for the entire experiment. Thirty-one weeks after AOM, rats treated with Synergy1 (PRE and PREPRO groups) had a significantly lower (P < 0.001) number of tumours (adenomas and cancers) than rats without Synergy1 (colorectal tumours/rat were 1.9 +/- 1.7, 1.1 +/- 1.1, 2.2 +/- 1.4 and 0.9 +/- 1.2 in Controls, PRE, PRO and PREPRO groups, respectively, means +/- SD). A slight, not significant effect of probiotics in reducing malignant tumours was also observed (P = 0.079). Caecal short-chain fatty acids (SCFA) were higher (P < 0.001) in the groups treated with Synergy1. Apoptosis was increased in the normal mucosa of the PRO group, while no variation was observed in the tumours. Colonic proliferation was lower in the PRE group as compared with Controls. Glutathione S-transferase placental enzyme pi type expression, and to a lesser extent, inducible NO synthase were depressed in the tumours from rats in the PRE and PREPRO groups. Cycloxygenase-2 expression was increased in the tumours of control rats but not in those from PRE, PRO or PREPRO rats. In conclusion, prebiotic administration in the diet decreases AOM-induced carcinogenesis in rats.
低聚果糖等益生元、乳酸杆菌或双歧杆菌等益生菌，或益生元与益生菌的组合（合生元）被认为对结肠癌具有保护作用。因此，我们研究了富含低聚果糖的益生元菊粉（商品名Raftilose-Synergy1，简称Synergy1，占饮食的10%）、益生菌[乳酸双歧杆菌（Bb12）和鼠李糖乳杆菌（LGG），各为5×10⁸ c.f.u./g饮食]或合生元（两者组合）是否能保护大鼠免受偶氮甲烷（AOM）诱导的结肠癌。雄性F344大鼠被分为：对照组；PRE组，喂食含Synergy1的饮食；PRO组，喂食含LGG和Bb12的饮食；PREPRO组，喂食含Synergy1、LGG和Bb12的饮食。开始饮食10天后，大鼠接受AOM处理（15 mg/kg皮下注射，共两次）；饮食处理持续整个实验。AOM处理31周后，接受Synergy1处理的大鼠（PRE组和PREPRO组）肿瘤（腺瘤和癌）数量显著低于未接受Synergy1处理的大鼠（对照组、PRE组、PRO组和PREPRO组每只大鼠的结直肠肿瘤数分别为1.9±1.7、1.1±1.1、2.2±1.4和0.9±1.2，均值±标准差）（P<0.001）。还观察到益生菌在减少恶性肿瘤方面有轻微但不显著的作用（P = 0.079）。接受Synergy1处理的组盲肠短链脂肪酸（SCFA）含量更高（P<0.001）。PRO组正常黏膜中的细胞凋亡增加，而肿瘤中未观察到变化。与对照组相比，PRE组的结肠增殖较低。PRE组和PREPRO组大鼠肿瘤中的谷胱甘肽S-转移酶胎盘型酶pi的表达以及诱导型一氧化氮合酶的表达在较小程度上受到抑制。对照组大鼠肿瘤中的环氧化酶-2表达增加，但PRE组、PRO组或PREPRO组大鼠肿瘤中的环氧化酶-2表达未增加。总之，饮食中给予益生元可降低大鼠中AOM诱导的致癌作用。
