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消痰散结方,一种复方中药,通过调节 GnT-V 介导的 E-钙黏蛋白糖基化抑制胃癌转移。

Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation.

机构信息

Department of Integrative Medicine, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200433, China.

Department of Obstetrics and Gynecology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.

出版信息

J Integr Med. 2023 Nov;21(6):561-574. doi: 10.1016/j.joim.2023.11.001. Epub 2023 Nov 7.

Abstract

OBJECTIVE

Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis.

METHODS

The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5).

RESULTS

The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment.

CONCLUSION

XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.

摘要

目的

消痰散结方(XTSJ)是一种中药复方,对胃癌(GC)转移具有显著的抑制作用。本研究旨在探讨 XTSJ 抑制 GC 转移的作用机制。

方法

采用 GC 细胞系,在体外研究 XTSJ 对 GC 转移的影响及相关机制,并在 GC 小鼠模型中,通过聚焦 Glc-N-Ac-transferase V(GnT-V;由 MGAT5 编码)的表达,研究 XTSJ 的作用机制。

结果

XTSJ 给药后 GC 细胞的迁移和侵袭能力明显下降,证实了 XTSJ 在体外治疗 GC 的疗效。XTSJ 增加了 GC 细胞间连接的 E-钙黏蛋白的积累,而 MGAT5 过表达则逆转了这一作用。XTSJ 给药和 MGAT5 敲低减轻了细胞-细胞连接的结构异常,而 MGAT5 过表达则产生相反的效果。MGAT5 敲低和 XTSJ 处理也显著增加了与 E-钙黏蛋白介导的黏着连接复合物相关的蛋白质的积累。此外,与 BGC-823-MGAT5+溶剂小鼠相比,BGC-823-MGAT5+XTSJ 小鼠肺部的 MGAT5 表达明显降低,表明 XTSJ 治疗后体内胃肿瘤向肺部转移的能力降低。

结论

XTSJ 通过抑制 GnT-V 介导的 E-钙黏蛋白糖基化和促进 E-钙黏蛋白在细胞-细胞连接处的积累,防止 GC 转移。请引用本文:Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. 消痰散结方,一种复方中药,通过调节 GnT-V 介导的 E-钙黏蛋白糖基化抑制胃癌转移。J 整合医学。2023;21(6):561-574.

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