清热化湿方通过上调miRNA-155 抑制Wnt/β-catenin信号通路治疗胃癌的作用机制研究  

Mechanism study of Qingre huashi decoction in the treatment of gastric cancer by up-regulating miRNA-155 and inhibiting Wnt/β-catenin signaling pathway

作　　者：尹硕鑫 敖先伟[2] 李博[3] 张涛[4] 陈远能[4] YIN Shuoxin;AO Xianwei;LI Bo;ZHANG Tao;CHEN Yuanneng(Nanyang Central Hospital,Henan Nanyang 473000,China;Dept.of Gastroenterology,the Second People’s Hospital of Jinzhou,Hubei Jinzhou 434000,China;Dept.of Respiratory Medicine,Nanyang Central Hospital,Henan Nanyang 473000,China;Dept.of Gastroenterology,Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530011,China)

机构地区：[1]南阳市中心医院,河南南阳473000 [2]荆州市第二人民医院消化内科,湖北荆州434000 [3]南阳市中心医院呼吸内科,河南南阳473000 [4]广西中医药大学附属瑞康医院消化内科,南宁530011

出　　处：《中国药房》2023年第19期2339-2343,共5页China Pharmacy

基　　金：广西自然科学基金项目(No.2020GXNSFAA238030);广西中医药大学研究生教育创新计划项目(No.YCSZ2022018)。

摘　　要：目的研究清热化湿方干预miRNA-155抑制Wnt/β-catenin信号通路治疗胃癌的作用机制。方法将30只裸鼠随机分为模型组、对照组(0.004g/kg顺铂+0.02g/kg氟尿嘧啶)、过表达组和清热化湿方低、中、高剂量组(2.71、5.43、10.86g/kg),每组5只。过表达组接种过表达miRNA-155AGS细胞,其余各组均接种AGS细胞,以复制胃癌荷瘤模型。对照组腹腔注射相应药物,其余各组灌胃相应药物或生理盐水,每天1次,连续3周。测定各组裸鼠的肿瘤组织质量,观察肿瘤组织的病理学形态,检测肿瘤组织中miRNA-155以及Wnt7、β-catenin、T细胞因子4(TCF-4)蛋白和mRNA表达水平。结果与模型组比较,对照组、过表达组及清热化湿方高剂量组裸鼠肿瘤组织质量均显著降低(P<0.05);Wnt7、β-catenin、TCF-4mRNA和蛋白表达水平均显著降低(P<0.05),miRNA-155表达水平均显著升高(P<0.05);肿瘤细胞均出现不同程度的排列疏松,核染色较浅,出现坏死灶。结论清热化湿方可通过上调miRNA-155,抑制Wnt/β-catenin信号通路中Wnt7、β-catenin、TCF-4mRNA和蛋白的表达,进而抑制胃癌荷瘤模型裸鼠的瘤体生长。OBJECTIVE To study the mechanism of Qingre huashi decoction in the treatment of gastric cancer by intervening in miRNA-155 and inhibiting Wnt/β-catenin signaling pathway.METHODS Thirty nude mice were randomly divided into model group,control group(0.004 g/kg cisplatin+0.02 g/kg fluorouracil),overexpression group,Qingre huashi prescription low-dose,medium-dose and high-dose groups(2.71,5.43,10.86 g/kg),with 5 mice in each group.The overexpression group was inoculated with miRNA-155 AGS cell line,and the other groups were inoculated with AGS cells to induce tumor-bearing gastric cancer model.The control group was given relevant medicine intraperitoneally,and other groups were given relevant medicine or normal saline intragastrically,once a day,for 3 consecutive weeks.The weight of tumor tissue in nude mice was determined;the pathological morphology of tumor tissue was observed;the miRNA-155 expression,mRNA and protein expressions of Wnt7,β-catenin and T-cell factor-4(TCF-4)in tumor tissue were detected.RESULTS Compared with the model group,the tumor weights of nude mice in the control group,the overexpression group and Qingre huashi decoction high-dose group were significantly reduced(P<0.05);mRNA and protein expressions of Wnt7,β-catenin and TCF-4 were significantly decreased(P<0.05),while miRNA-155 expression was increased significantly(P<0.05).Tumor cells exhibited varying degrees of loose arrangement,shallow nuclear staining,and necrotic foci.CONCLUSIONS Qingre huashi decoction can inhibit the protein and mRNA expressions of Wnt7,β-catenin and TCF-4 in Wnt/β-catenin signaling pathway by up-regulating miRNA-155,thus inhibiting the tumor growth of tumor-bearing nude mice.

关 键 词：清热化湿方 miRNA-155 胃癌 Wnt7 Β-CATENIN T细胞因子4 

分 类 号：R965[医药卫生—药理学]