目的：探究桃叶珊瑚苷（AU）调控RhoA/ROCK 信号通路对胃癌MGC803 细胞上皮间质转化（EMT）进程和血管生成拟态（VM）形成的影响。方法：常规培养人胃癌MGC803 细胞，将其随机分为对照组、AU-L 组（20 μmol/L AU）、AU-M 组（40 μmol/L AU）、AU-H组（80 μmol/L AU）、AU-H+RhoA 激活剂水仙环素（Nar）组（AU-H+Nar 组，80 μmol/L AU+30 μmol/L Nar）。采用CCK-8法、Transwell 实验、细胞划痕实验分别检测不同浓度AU对细胞增殖、迁移和侵袭的影响，三维细胞培养法观察不同浓度AU对细胞体外VM管腔结构形成的影响，WB法检测AU对各组细胞RhoA、ROCK、VM与EMT相关蛋白表达的影响。结果：与对照组相比，AU-M组、AU-H组MGC803 细胞增殖率（48、72 h时）、细胞迁移率、细胞侵袭数目、VM 管腔结构数，以及RhoA、 ROCK1、N-cadherin、vimentin、VE-cadherin 的蛋白表达均显著降低（均P<0.05），E-cadherin 表达显著升高（P<0.05）；同时，使用Nar处理显著减弱了AU对MGC803 细胞EMT和VM形成的抑制作用（均P<0.05）。结论：AU通过下调RhoA/ROCK 信号通路抑制胃癌MGC803细胞的增殖、迁移、侵袭、EMT和VM形成过程。

Objective: To investigate the effects of aucubin (AU) on epithelial interstitial transformation (EMT) and vasculogenic mimicry (VM) formation in gastric cancer MGC803 cells by regulating the RhoA/ROCK signaling pathway. Methods: Human gastric cancer MGC803 cells were routinely cultured and randomly divided into the Control group, the AU-L group (20 μmol/L AU), the AU-M group (40 μmol/L AU), the AU-H group (80 μmol/L AU), and the AU-H+RhoA activator naciclassine (Nar) group (AU-H+Nar group, 80 μmol/L AU+30 μmol/L Nar). The effects of AU on cell proliferation, invasion and migration were detected by CCK-8 assay, Transwell assay and cell scratch assay, respectively. Three-dimensional cell culture was applied to observe the effects of different concentration of AU on the formation of VM lumen in vitro in each group. The effects of different concentration of AU on the expressions of RhoA, ROCK, VM, and EMT related proteins in each group were detected by Western blot. Results: Compared with those in the Control group, the proliferation rates (48 and 72 h), the cell migration rate, the number of cell invasions, the number of VM lumen structures, the protein expressions of RhoA, ROCK1, N-cadherin, vimentin, and VE cadherin in MGC803 cells in the AU-M and AU-H groups reduced significantly (all P<0.05). The expression of E-cadherin increased significantly (P<0.05). Simultaneous use of Nar significantly weakened the inhibitory effect of AU on EMT and VM formation in MGC803 cells (all P<0.05). Conclusion: AU inhibits the proliferation, migration, invasion, EMT and VM formation processes of gastric cancer MGC803 cells by down-regulating the RhoA/ROCK signaling pathway.

湖北省中医药管理局中医药科研项目（No. ZY2023F061）