黄芪总皂苷调控Wnt3a/β-catenin/EMT通路抑制结肠癌肝转移的作用机制  

Mechanism of total Astragalus saponins regulating Wnt3a/β-catenin/EMT pathway to inhibit liver metastasis of colon cancer

作　　者：王旭[1] 万林鹭 殷启航 孙若岚 顾俊菲[1,2] 唐德才 WANG Xu;WAN Linlu;YIN Qihang;SUN Ruolan;GU Junfei;TANG Decai(School of Traditional Chinese Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Key Laboratory for High Technology Research of TCM Formulae,Nanjing 210023,China)

机构地区：[1]南京中医药大学中医学院,南京210023 [2]江苏省方剂研究重点实验室,南京210023

出　　处：《中华中医药杂志》2024年第4期1763-1768,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.81904059);南京中医药大学青年基金项目(No.NZY81904059);国家自然科学基金面上项目(No.82274116);江苏省中医药科技发展专项(No.2020ZX01)。

摘　　要：目的:观察黄芪总皂苷对小鼠结肠癌肝转移的抑制作用,并探讨其通过调节Wnt3a/β-catenin/EMT通路发挥抑制作用的相关机制。方法:用CT26.WT细胞构建结肠癌原位移植瘤小鼠模型,将50只BA L B/c小鼠随机分为假手术组、模型组、阳性对照组、黄芪总皂苷低剂量组(50 m g·k g^(-1)·d^(-1))、黄芪总皂苷高剂量组(100 mg·kg^(-1)·d^(-1)),每组10只。取各组小鼠肝脏组织,观察结肠肿瘤肝转移情况,采用HE染色观察肝组织病理形态学变化,Western Blot检测Wnt3a/β-catenin/EMT相关蛋白的表达,免疫荧光染色检测β-catenin蛋白在肝组织中的表达情况。结果:模型组小鼠肝脏出现明显转移结节,且病理变化较明显,尤其出现较多肿瘤细胞浸润情况。与模型组比较,黄芪总皂苷高剂量组及阳性对照组小鼠肝组织转移灶数量明显减少,肝脏病理得到明显改善,肿瘤细胞浸润明显减少,肝组织中Wnt3a、β-catenin、N-cadherin、Vimentin蛋白表达量显著降低(P<0.05,P<0.01),GSK3β和E-cadherin蛋白表达量显著升高(P<0.05)。结论:黄芪总皂苷可能通过调控肝组织中Wnt3a/β-catenin/EMT信号通路发挥抑制结肠癌原位移植瘤小鼠肝转移的作用。Objective:To observe the inhibitory effect of total Astragalus saponins(TAS)on liver metastasis of colon cancer in mice,and to explore the mechanism by which TAS regulate the Wnt3a/β-catenin/EMT pathway to exert this inhibitory effect.Methods:CT26.WT cells were used to construct a orthotopic transplantation mice model of colon cancer.A total of 50 BALB/c mice were randomly divided into sham operation group,model group,positive control group,total astragalus saponins low-dose group(50 mg·kg^(-1)·d^(-1)),and total astragalus saponins high-dose group(100 mg·kg^(-1)·d^(-1)),with 10 mice in each group.Liver tissue were taken to observe liver metastasis of colon cancer.HE stain was used for histopathological morphology observation,Western Blot was used to measure the expression levels of Wnt3a/β-catenin/EMT related proteins,and immunofluorescence staining was used to assess the expression ofβ-catenin protein.Results:Obvious metastatic nodules appeared in the livers of mice in the model group,and pathological changes were more obvious,especially more tumor cell infiltration.Compared with the model group,the total astragalus saponins high-dose group and the positive control group showed a significant reduction in the number of liver metastases,a significant improvement in liver pathology,a significant reduction in tumor cell infiltration.Additionally,the protein expression of Wnt3a,β-catenin,N-cadherin,and Vimentin in liver tissue was significantly reduced(P<0.05,P<0.01),and the expression of GSK3βand E-cadherin protein was significantly increased(P<0.05).Conclusion:TAS may inhibit liver metastasis in colon cancer orthotopic transplantation mice models by regulating the Wnt3a/β-catenin/EMT signaling pathway in liver tissue.

关 键 词：黄芪总皂苷 结肠癌 肝转移 Wnt3a/β-catenin 上皮-间充质转化 

分 类 号：R285.5[医药卫生—中药学]