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.

中文翻译：

---

消痰散结方通过调节GnT-V介导的E-钙粘蛋白糖基化抑制胃癌转移

客观的

消痰散结方（XTSJ）是一种中药复方药物，对胃癌（GC）转移具有显着的抑制作用。这项工作研究了 XTSJ 介导的 GC 转移抑制机制。

方法

通过关注Glc - N-Ac-转移酶 V (GnT-V ;由MGAT5编码）。

结果

XTSJ给药后GC细胞的迁移和侵袭能力显着下降，证实了XTSJ在体外治疗GC的功效。XTSJ 增加了 GC 细胞之间连接处 E-钙粘蛋白的积累，MGAT5过表达可逆转这一现象。XTSJ 给药和MGAT5敲低减轻了细胞-细胞连接的结构异常，而MGAT5过表达则具有相反的效果。MGAT5敲除和 XTSJ 治疗还显着增加了与 E-钙粘蛋白介导的粘附连接复合物相关的蛋白质的积累。此外，BGC-823- MGAT5 +XTSJ小鼠肺部MGAT5的表达显着低于 BGC-823- MGAT5 +溶剂小鼠，表明体内 胃肿瘤向肺部转移的能力降低XTSJ 治疗后。

结论

XTSJ 通过抑制 GnT-V 介导的 E-钙粘蛋白糖基化并促进 E-钙粘蛋白在细胞-细胞连接处的积累来预防 GC 转移。

引用该文章为：黄宁，何红伟，何YY，顾伟，徐明军，刘L。消痰散结方是一种复方中药，通过调节GnT-V介导的E-钙粘蛋白糖基化抑制胃癌转移。整合医学杂志。2023；21（6）：561-574。