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莪术醇对产肠毒素(ETBF)定植 AOM/DSS BALB/c 小鼠结肠肿瘤发生的保护作用。

Protective Effects of Zerumbone on Colonic Tumorigenesis in Enterotoxigenic (ETBF)-Colonized AOM/DSS BALB/c Mice.

机构信息

Department of Biomedical Laboratory Science, College of Health Sciences, MIRAE Campus, Yonsei University, Wonju, Gangwon-do 26493, Korea.

Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 26426, Korea.

出版信息

Int J Mol Sci. 2020 Jan 29;21(3):857. doi: 10.3390/ijms21030857.

DOI:10.3390/ijms21030857
PMID:32013191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7036928/
Abstract

Chronic inflammation has been linked to colitis-associated colorectal cancer in humans. The human symbiont enterotoxigenic Bacteroides fragilis (ETBF), a pro-carcinogenic bacterium, has the potential to initiate and/or promote colorectal cancer. Antibiotic treatment of ETBF has shown promise in decreasing colonic polyp formation in murine models of colon cancer. However, there are no reported natural products that have shown efficacy in decreasing polyp burden. In this study, we investigated the chemopreventive effects of oral administration of zerumbone in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. Zerumbone significantly reduced the severity of disease activity index (DAI) scores as well as several parameters of colonic inflammation (i.e., colon weight, colon length, cecum weight and spleen weight). In addition, inflammation of the colon and cecum as well as hyperplasia was reduced. Zerumbone treatment significantly inhibited colonic polyp numbers and prevented macroadenoma progression. Taken together, these findings suggest that oral treatment with zerumbone inhibited ETBF-promoted colon carcinogenesis in mice indicating that zerumbone could be employed as a promising protective agent against ETBF-mediated colorectal cancer.

摘要

慢性炎症与人类结肠炎相关的结直肠癌有关。人类共生肠产毒脆弱拟杆菌(ETBF)是一种致癌前细菌,具有引发和/或促进结直肠癌的潜力。抗生素治疗 ETBF 已显示出在减少结肠癌小鼠模型中结肠息肉形成方面的潜力。然而,目前尚无报道表明天然产物在减少息肉负担方面具有疗效。在这项研究中,我们研究了莪术醇在 ETBF 定植的小鼠中通过氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导肿瘤发生的化学预防作用。莪术醇显著降低了疾病活动指数(DAI)评分的严重程度以及几种结肠炎症参数(即结肠重量、结肠长度、盲肠重量和脾脏重量)。此外,还减轻了结肠和盲肠的炎症和增生。莪术醇治疗显著抑制了结肠息肉数量并阻止了大腺瘤的进展。综上所述,这些发现表明莪术醇的口服治疗抑制了 ETBF 促进的小鼠结肠癌发生,表明莪术醇可用作预防 ETBF 介导的结直肠癌的有前途的保护剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e36/7036928/07dca666b55a/ijms-21-00857-g006.jpg
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Intestinal Epithelial Cells Exposed to Bacteroides fragilis Enterotoxin Regulate NF-κB Activation and Inflammatory Responses through β-Catenin Expression.
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