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唾液乳杆菌 REN 抑制 4-硝基喹啉 1-氧化物诱导的大鼠口腔癌。

Lactobacillus salivarius REN inhibits rat oral cancer induced by 4-nitroquioline 1-oxide.

机构信息

Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

出版信息

Cancer Prev Res (Phila). 2013 Jul;6(7):686-94. doi: 10.1158/1940-6207.CAPR-12-0427. Epub 2013 May 8.

Abstract

Despite significant advances in cancer therapy, cancer-related mobility and mortality are still rising. Alternative strategies such as cancer prevention thus become essential. Probiotics represent an emerging option for cancer prevention, but studies are limited to colon cancers. The efficiency of probiotics in the prevention of other cancers and the correlative mechanism remains to be explored. A novel probiotics Lactobacillus salivarius REN (L. salivarius REN) was isolated from centenarians at Bama of China, which showed highly potent antigenotoxicity in an initial assay. 4-nitroquioline 1-oxide (4NQO)-induced oral cancer model was introduced to study the anticancer activity of L. salivarius REN in vivo. The results indicated that oral administration of probiotic L. salivarius REN or its secretions could effectively suppress 4NQO-induced oral carcinogenesis in the initial and postinitial stage, and the inhibition was in a dose-dependent manner. A significant decrease of neoplasm incidence (65%-0%) was detected in rats fed with the high dose of L. salivarius REN [5 × 10(10) CFU/kg body weight (bw)/d]. In vivo evidences indicated that the probiotics inhibited 4NQO-induced oral cancer by protecting DNA against oxidative damage and downregulating COX-2 expression. L. salivarius REN treatment significantly decreased the expression of proliferating cell nuclear antigen (PCNA) and induced apoptosis in a dose-dependent manner. Our findings suggest that probiotics may act as potential agents for oral cancer prevention. This is the first report showing the inhibitory effect of the probiotics on oral carcinogenesis.

摘要

尽管癌症治疗取得了重大进展,但癌症相关的活动能力丧失和死亡率仍在上升。因此,癌症预防等替代策略变得至关重要。益生菌是癌症预防的一种新兴选择,但研究仅限于结肠癌。益生菌在预防其他癌症中的效率及其相关机制仍有待探索。一种新型益生菌唾液乳杆菌 REN(L. salivarius REN)从中国巴马的百岁老人中分离出来,在初步试验中表现出很强的抗原毒性。本研究采用 4-硝基喹啉 1-氧化物(4NQO)诱导的口腔癌模型,研究 L. salivarius REN 在体内的抗癌活性。结果表明,益生菌 L. salivarius REN 或其分泌物的口服给药可有效抑制 4NQO 诱导的口腔癌发生的初始和后期阶段,且抑制作用呈剂量依赖性。高剂量 L. salivarius REN[5×10(10)CFU/kg 体重(bw)/d]喂养的大鼠中,肿瘤发生率显著降低(65%-0%)。体内证据表明,益生菌通过保护 DNA 免受氧化损伤和下调 COX-2 表达来抑制 4NQO 诱导的口腔癌。L. salivarius REN 处理可显著降低增殖细胞核抗原(PCNA)的表达,并呈剂量依赖性诱导细胞凋亡。我们的研究结果表明,益生菌可能是口腔癌预防的潜在药物。这是首次报道益生菌对口腔癌发生的抑制作用。

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