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
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篇名: 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
TITLE: Mechanism study of Qingre huashi decoction in the treatment of gastric cancer by up-regulating miRNA-155 and inhibiting Wnt/β-catenin signaling pathway
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。
ABSTRACT: 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.
期刊: 2023年第34卷第19期
作者: 尹硕鑫;敖先伟;李博;张涛;陈远能
AUTHORS: YIN Shuoxin,AO Xianwei,LI Bo,ZHANG Tao,CHEN Yuanneng
关键字: 清热化湿方;miRNA-155;胃癌;Wnt7;β-catenin;T细胞因子4
KEYWORDS: Qingre huashi decoction; miRNA-155; gastric
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