目的 基于转化生长因子-β（transforming growth factor-β，TGF-β）/Smad信号通路和上皮间充质转化（epithelial-mesenchymal transition，EMT）探讨黄芪多糖（Astragalus polysaccharides，APS）抑制结直肠癌肝转移的作用及机制。方法 小鼠脾脏注射结直肠癌MC-38细胞建立结直肠癌肝转移模型，造模成功后随机模型组、5-氟尿嘧啶（5-fluorouracil，5-FU）组和黄芪多糖低、中、高剂量组。连续给药21 d后，通过活体成像仪评估肝转移情况；收集小鼠血清和肝脏组织，采用苏木素-伊红（HE）染色考察肝脏组织病理变化，采用ELISA试剂盒检测血清中白细胞介素-1β（interleukin-1β，IL-1β）、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平，采用qRT-PCR检测肝脏组织EMT相关基因表达，采用Western blotting检测肝脏组织TGF-β/Smad信号通路和EMT相关蛋白表达。结果 与模型组比较，黄芪多糖组小鼠肝脏转移灶明显减少（P＜0.05），肝脏组织结构较完整，血清中炎性因子水平显著降低（P＜0.05），肝脏组织TGF-β、Smad2、Smad3、N-cadherin、Vimentin表达显著降低（P＜0.05），E-cadherin表达显著升高（P＜0.05）。结论 黄芪多糖通过调控TGF-β/Smad信号通路，抑制炎症反应及EMT过程，从而抑制结直肠癌的肝转移。

Objective To explore the effect and mechanism of Astragalus polysaccharides (APS) on inhibiting liver metastasis of colorectal cancer based on transforming growth factor-β (TGF-β)/Smad signaling pathway and epithelial-mesenchymal transition (EMT). Methods A colorectal cancer liver metastasis model was established by injecting MC-38 cells into the spleen of mice. After successful modeling, model group, 5-fluorouracil (5-FU) group, and APS low-, medium-, high-dose groups were randomly selected. After 21 d of continuous administration, liver metastasis was evaluated using a live imaging device; Serum and liver tissue were collected, the pathological changes of liver tissue was investigated using hematoxylin eosin (HE) staining, the levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in serum were detected using ELISA kit, the expressions of EMT-related genes in liver tissue were detected using qRT-PCR, the expressions of TGF-β/Smad signaling pathway and EMT-related proteins in liver tissue were detected using Western blotting. Results Compared with model group, APS group showed a significant reduction in liver metastases (P < 0.05) and a more complete liver tissue structure, levels of inflammatory factors in serum were significantly decreased (P < 0.05), expressions of TGF-β, Smad2, Smad3, N-cadherin and Vimentin in liver tissue were significantly decreased (P < 0.05), while the expression of E-cadherin was significantly increased (P < 0.05). Conclusion APS inhibits liver metastasis of colorectal cancer by regulating TGF-β/Smad signaling pathway, suppressing inflammatory response and EMT process.

R285.5

河南省中医药科学研究专项课题（2021JDZY026）;河南中医药学科领军人才项目（豫卫中医函[2021]8号）;河南省自然科学基金项目（222300420489）