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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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尹硕鑫 ,敖先伟 ,李 博 ,张 涛 ,陈远能 (1.南阳市中心医院,河南 南阳 473000;2.荆州市第二人民医
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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)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2023)19-2339-05
DOI 10.6039/j.issn.1001-0408.2023.19.07
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(0.004 g/kg顺铂+0.02 g/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、10.86 g/kg),每组5只。
过表达组接种过表达miRNA-155 AGS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-4 mRNA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-4 mRNA和蛋白的表达,进而抑制胃癌荷瘤模型裸鼠
的瘤体生长。
关键词 清热化湿方;miRNA-155;胃癌;Wnt7;β-catenin;T细胞因子4
Mechanism study of Qingre huashi decoction in the treatment of gastric cancer by up-regulating miRNA-
155 and inhibiting Wnt/β-catenin signaling pathway
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YIN Shuoxin ,AO Xianwei ,LI Bo ,ZHANG Tao ,CHEN Yuanneng(1. Nanyang Central Hospital, Henan
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Nanyang 473000, China;2. Dept. of Gastroenterology, the Second People’s Hospital of Jinzhou, Hubei Jinzhou
434000, China;3. Dept. of Respiratory Medicine, Nanyang Central Hospital, Henan Nanyang 473000, China;
4. Dept. of Gastroenterology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning
530011, China)
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-
Δ 基金项目 广西自然科学基金项目(No.2020GXNSFAA238030);
regulating miRNA-155, thus inhibiting the tumor growth of
广西中医药大学研究生教育创新计划项目(No.YCSZ2022018)
*第一作者 硕士。研究方向:消化系统肿瘤的研究和诊治。 tumor-bearing nude mice.
E-mail:ysx005512@163.com KEYWORDS Qingre huashi decoction; miRNA-155; gastric
# 通信作者 教授,博士。研究方向:消化系统疾病的研究和诊治。 cancer; Wnt7; β-catenin; T-cell factor-4
E-mail:cyn60668@aliyun.com
中国药房 2023年第34卷第19期 China Pharmacy 2023 Vol. 34 No. 19 · 2339 ·