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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
                          2
                 1*
                                  3
                                           4
          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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                                                        4
                                   2
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          YIN Shuoxin ,AO Xianwei ,LI Bo ,ZHANG Tao ,CHEN Yuanneng(1.  Nanyang  Central  Hospital,  Henan
                                                                         4
          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 ·
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