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密花八角抑制 Lgr5 表达对胃癌前病变大鼠胃黏膜上皮细胞上皮间质转化的影响。

Effects of Celastrus orbiculatus on Epithelial Mesenchymal Transition in Gastric Mucosal Epithelial Cells by Inhibiting Lgr5 Expression from Rats with Gastric Precancerous Lesions.

机构信息

* Department of Chinese Integrative Medicine Oncology, First Affiliated Hospital of Medical University of Anhui, Hefei, Anhui, P. R. China.

† Chinese Medical Institution, Yangzhou University, Yangzhou, Jiangsu, P. R. China.

出版信息

Am J Chin Med. 2018;46(5):1129-1143. doi: 10.1142/S0192415X18500593. Epub 2018 Jul 5.

Abstract

The extract of Celastrus orbiculatus (COE) has been shown to possess anti-Helicobacter pylori (H. pylori) activity and anticancer effects in vitro and in vivo. However, the molecular mechanism by which COE on precancerous lesions of gastric cancer (PLGC) has not been fully elucidated so far. The purpose of this study is to evaluate the effect and mechanism of COE in the rat model of PLGC, after the rat model of PLGC was successfully constructed. The effects of COE in gastric mucosa of rats with PLGC were tested using routine pathology and a transmission electron microscope (TEM) analysis. The protein and mRNA expression levels of epithelial mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and Vimentin) and leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) were detected adopting techniques of immunohistochemistry (IHC), real-time PCR (RT-PCR) and western blot assays. The body weight of PLGC rats was significantly higher in the COE group than that in the untreated group. The process of PLGC was significantly reversed after COE treatment, shown by observing the changes of histopathological morphology and ultrastructure. Gastric mucosal epithelial cells in COE high dose (COE-H) group showed significantly higher expression levels of E-cadherin, and lower expression levels of N-cadherin, Vimentin and Lgr5 than those of the untreated group. COE could suppress the spatial distribution of Lgr5[Formula: see text] cell changes in PLGC rats. These findings suggested that the therapeutic mechanisms of COE in treating PLGC might be related with its effects on reversing the EMT process and inhibiting Lgr5 expression.

摘要

三叶木通提取物(COE)已被证明具有抗幽门螺杆菌(H. pylori)的体外和体内活性和抗癌作用。然而,COE 对胃癌前病变(PLGC)的分子机制迄今尚未完全阐明。本研究旨在评估 COE 在成功构建 PLGC 大鼠模型后的 PLGC 大鼠模型中的作用和机制。采用常规病理学和透射电子显微镜(TEM)分析检测 COE 对 PLGC 大鼠胃黏膜的影响。采用免疫组织化学(IHC)、实时 PCR(RT-PCR)和 Western blot 检测上皮间质转化(EMT)标志物(E-钙黏蛋白、N-钙黏蛋白和波形蛋白)和富含亮氨酸重复的 G 蛋白偶联受体 5(Lgr5)的蛋白和 mRNA 表达水平。COE 组 PLGC 大鼠体重明显高于未治疗组。COE 治疗后 PLGC 过程明显逆转,通过观察组织病理学形态和超微结构的变化可以看出。COE 高剂量(COE-H)组胃黏膜上皮细胞中 E-钙黏蛋白表达水平明显升高,N-钙黏蛋白、波形蛋白和 Lgr5 表达水平明显低于未治疗组。COE 可抑制 Lgr5[Formula: see text]细胞在 PLGC 大鼠中的空间分布变化。这些发现表明,COE 治疗 PLGC 的治疗机制可能与其逆转 EMT 过程和抑制 Lgr5 表达的作用有关。

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