阿克曼菌对AOM/DSS炎症相关性结直肠癌发生的作用  

Effects of Akkermansia on AOM/DSS Inflammatory-associated Colorectal Cancer

作　　者：张璐 刘铄川 王琦珂 姬高 武艺铭 杨利梅 隋华 刘怀民 ZHANG Lu;LIU Shuochuan;WANG Qike;JI Gao;WU Yiming;YANG Limei;SUI Hua;LIU Huaimin(Department of Integrated Traditional Chinese and Western Medicine,The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer Hospital,Zhengzhou 450008,China;Graduate School,The Second Affiliated Hospital of Henan University of Chinese Medicine&Henan Province Hospital of TCM,Zhengzhou 450003,China;Department of Medical Oncology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Research Center of Translational Medicine for Cancer Prevention,Jiading Branch of Shanghai First People’s Hospital,Shanghai 201803,China)

机构地区：[1]郑州大学附属肿瘤医院(河南省肿瘤医院)中西医结合科,郑州450008 [2]河南中医药大学第二附属医院(河南省中医院)研究生院,郑州450003 [3]上海中医药大学附属曙光医院肿瘤科,上海201203 [4]上海市第一人民医院嘉定分院,肿瘤防治转化医学研究中心,上海201803

出　　处：《肿瘤防治研究》2023年第4期351-356,共6页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金联合项目(U2004105);河南省中医药科学研究专项课题重大专项(20-21ZYZD07);河南省中医药科学研究专项课题(2022ZY1223)

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。Objective To 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.Methods AOM/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.Results Compared 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.Conclusion AKK 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.

关 键 词：结直肠癌 阿克曼菌 肠道菌群 肠道干细胞 

分 类 号：R735.3[医药卫生—肿瘤]