Departamento de Salud, El Colegio de La Frontera Sur, Periférico Sur s/n, María Auxiliadora, 29290, San Cristóbal de Las Casas, Chiapas, Mexico.
Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Carretera Guadalajara-Nogales Km 15.5, Las Agujas, C.P. 45110, Zapopan, Jalisco, Mexico.
Probiotics Antimicrob Proteins. 2017 Jun;9(2):163-171. doi: 10.1007/s12602-017-9253-2.
The administration of probiotics is a promising approach to reduce the prevalence of colon cancer, a multifactorial disease, with hereditary factors, as well as environmental lifestyle-related risk factors. Biogenic polyamines, putrescine, spermidine, and spermine are small cationic molecules with great roles in cell proliferation and differentiation as well as regulation of gene expression. Ornithine decarboxylase is the first rate-limiting enzyme for polyamine synthesis, and upregulation of ornithine decarboxylase activity and polyamine metabolism has been associated with abnormal cell proliferation. This paper is focused on studying the protective role of Lactobacillus casei ATCC 393 in a chemically induced mouse model of colon carcinogenesis, directing our attention on aberrant crypt foci as preneoplastic markers, and on polyamine metabolism as a possible key player in carcinogenesis. BALB/c mice were administered 1,2-dimethylhydrazine dihydrochloride (DMH) to induce colon cancer (20 mg/kg body weight, subcutaneous, twice a week for 24 weeks). L. casei ATCC 393 was given orally (10 CFU, twice a week), 2 weeks before DMH administration. Hematoxylin and eosin staining, high-performance liquid chromatography, and Western blotting were used to evaluate aberrant crypt foci, urinary polyamines, and ornithine decarboxylase expression in the colon. The experimental data showed that the preventive administration of L. casei ATCC 393 may delay the onset of cancer as it significantly reduced the number of DMH-induced aberrant crypt foci, the levels of putrescine, and the expression of ornithine decarboxylase. Hence, this probiotic strain has a prospective role in protection against colon carcinogenesis, and its antimutagenic activity may be associated with the maintenance of polyamine metabolism.
益生菌的应用是减少结直肠癌发病率的一种很有前景的方法，结直肠癌是一种多因素疾病，具有遗传因素以及环境生活方式相关的风险因素。生物源多胺（腐胺、亚精胺和精胺）是带有正电荷的小分子，在细胞增殖和分化以及基因表达调控方面具有重要作用。鸟氨酸脱羧酶是多胺合成的第一个限速酶，鸟氨酸脱羧酶活性和多胺代谢的上调与异常细胞增殖有关。本文重点研究干酪乳杆菌 ATCC 393 在化学诱导的结直肠癌变小鼠模型中的保护作用，将注意力集中在异常隐窝病灶作为癌前标志物，以及多胺代谢作为癌变的一个可能关键因素。BALB/c 小鼠给予 1,2-二甲基肼二盐酸盐（DMH）诱导结肠癌（20mg/kg 体重，皮下，每周两次，共 24 周）。在 DMH 给药前 2 周，给予干酪乳杆菌 ATCC 393 口服（10CFU，每周两次）。使用苏木精和伊红染色、高效液相色谱和 Western blot 评估结肠中的异常隐窝病灶、尿多胺和鸟氨酸脱羧酶表达。实验数据表明，干酪乳杆菌 ATCC 393 的预防性给药可能会延迟癌症的发生，因为它显著减少了 DMH 诱导的异常隐窝病灶的数量、腐胺水平和鸟氨酸脱羧酶的表达。因此，这种益生菌菌株在预防结直肠癌变方面具有潜在作用，其抗诱变活性可能与多胺代谢的维持有关。
