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摘要:目的
探讨阿克曼菌(AKK)对氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的炎症相关性结直肠癌小鼠模型及其肠道干细胞的影响。
方法AOM/DSS诱导小鼠炎症相关性结直肠癌模型随机分为三组，通过灌胃方式给予三组不同的药物分别为模型组(Model)、AKK组及阿司匹林组(Aspirin)。干预10周后观察小鼠的肿瘤数目、肿瘤大小、肿瘤分布及分析肿瘤负荷情况。免疫组织化学分析表征肿瘤恶性化的蛋白Ki67和表征干细胞的特异性蛋白Lgr5的表达变化。qRT-PCR检测干细胞分化特性的基因Lgr5、CD133、Nanog和ALDH1的mRNA表达。
结果与模型组相比，AKK组的肿瘤数目、肿瘤大小及肿瘤负荷明显减小(P < 0.01)；相较于模型组小鼠，AKK组的肿瘤组织中Ki67和Lgr5表达明显下降(P < 0.05)；CD133、Nanog和ALDH1的mRNA表达明显下调。
结论AKK对AOM/DSS诱导的结肠炎相关性结直肠癌小鼠具有防治作用，其作用机制可能与结直肠干细胞活性密切相关。
Abstract:ObjectiveTo investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells.
MethodsAOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR.
ResultsCompared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated.
ConclusionAKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.
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Key words:
- Colorectal cancer /
- Akkermansia /
- Intestinal flora /
- Intestinal stem cell
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Competing interests: The authors declare that they have no competing interests.利益冲突声明：所有作者均声明不存在利益冲突。作者贡献：张璐：课题设计、文章撰写刘铄川、王琦珂：实验实施姬高：数据统计武艺铭、杨利梅：实验实施隋华：实验指导刘怀民：实验设计与指导
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图 1 各组小鼠肠道腺瘤肿瘤数量比较
Figure 1 Comparison of the number of intestinal adenoma tumors in each group of mice
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图 2 各组小鼠肠道腺瘤肿瘤负荷比较
Figure 2 Comparison of tumor burden of intestinal adenoma in each group of mice
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图 3 各组小鼠肠道腺瘤Ki67蛋白表达(IHC ×200)
Figure 3 Expression of Ki67 protein in intestinal adenoma of mice in each group (IHC ×200)
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图 4 各组小鼠肠道腺瘤Lgr5蛋白表达(IHC ×200)
Figure 4 Expression of Lgr5 protein in intestinal adenoma of mice in each group (IHC ×200)
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图 5 AKK干预后AOM/DSS小鼠肠组织Lgr5、ALDH1、CD133、Nanog基因mRNA的表达
Figure 5 mRNA expressions of Lgr5, CD133, Nanog and ALDH1 in intestinal tissue of AOM/DSS mice after AKK intervention
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图 6 各组小鼠肠道腺瘤Lgr5的表达
Figure 6 Expression of Lgr5 in intestinal adenoma of mice in each group
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