蒺藜皂苷通过调控Wnt3a/β-catenin信号通路抑制胃癌细胞增殖、迁移侵袭的机制研究  

Tribulus saponins inhibit proliferation,migration,and invasion of gastric cancer cells by regulating Wnt3a/β-catenin signaling pathway

作　　者：曹斌 姚林华[2] 冯昕 Bin Cao;Lin-Hua Yao;Xin Feng(Department of Pharmacy,Huzhou First People’s Hospital,Huzhou 313000,Zhejiang Province,China;Department of Gastroenterology,Huzhou First People’s Hospital,Huzhou 313000,Zhejiang Province,China;Department of Infection,The Third People’s Hospital of Huzhou City,Huzhou 313000,Zhejiang Province,China)

机构地区：[1]湖州市第一人民医院药剂科,浙江省湖州市313000 [2]湖州市第一人民医院消化内科,浙江省湖州市313000 [3]湖州市第三人民医院院感科,浙江省湖州市313000

出　　处：《世界华人消化杂志》2022年第4期191-197,共7页World Chinese Journal of Digestology

摘　　要：背景蒺藜皂苷是从中药蒺藜内提取的活性成分,具有抗癌、抗炎、调节免疫、等多种药理活性,已有研究表明蒺藜皂苷能抑制胃癌细胞生长和诱导凋亡,本研究主要探究蒺藜皂苷可能抑制胃癌细胞增殖、迁移和侵袭.目的探讨蒺藜皂苷通过调控Wnt3a/β-catenin信号通路抑制胃癌细胞增殖、迁移侵袭的机制研究.方法以胃癌细胞HGC-27为体外研究对象,用浓度0、20 mg/L、40 mg/L蒺藜皂苷进行处理,记为对照组(Control)、蒺藜皂苷20 mg/L组、蒺藜皂苷40 mg/L组;将siRNA NC、siRNA Wnt3a转染胃癌细胞中,用40 mg/L蒺藜皂苷处理,记为蒺藜皂苷+siRNA NC组、蒺藜皂苷+siRNA Wnt3a组.用噻唑蓝(methylthiazolyldiphenyl-tetrazolium bromide,MTT)检测细胞增殖活性;伤口愈合实验检测细胞迁移;Transwell小室检测细胞侵袭;蛋白免疫印迹法(Western blot)检测p21、细胞增殖核抗原-67(proliferating nuclear antigen-67,Ki67)、上皮性钙黏附素(epithelical cadherin,E-cadherin)、神经性钙黏附素(neural cadherin,N-cadherin)、波形蛋白(Vimentin)、Wnt3a、β-catenin蛋白表达.结果与Control组比较,蒺藜皂苷20 mg/L组、蒺藜皂苷40 mg/L组胃癌细胞活性、迁移率、侵袭细胞数显著降低,p21、E-cadherin蛋白表达增加,Ki67、N-cadherin、Vimentin、Wnt3a、β-catenin蛋白表达降低.与蒺藜皂苷+siRNA NC组组相比,蒺藜皂苷+siRNA Wnt3a组胃癌细胞活性、迁移率、侵袭细胞数显著降低,Wnt3a、β-catenin、Ki67、N-cadherin、Vimentin蛋白表达降低,p21、E-cadherin蛋白表达增加.结论蒺藜皂苷可能通过抑制Wnt3a/β-catenin信号通路抑制胃癌细胞增殖、迁移、侵袭和上皮间质转化.BACKGROUND Tribulus terrestris saponins are active ingredients extracted from the traditional Chinese medicine tribulus terrestris,which have anti-cancer,anti-inflammatory,immune regulation,and other pharmacological activities.Studies have shown that tribulus terrestris saponins can inhibit the growth of gastric cancer cells and induce apoptosis.AIM To investigate the mechanism of tribulus terrestris saponins to inhibit the proliferation,migration,and invasion of gastric cancer cells.METHODS Gastric cancer cell line HGC-27 was used in this study.HGC-27 cells were treated with 0,20 mg/L,and 40 mg/L tribulus terrestris saponins.Meanwhile,HGC-27 cells were transfected with Wnt3a siRNA and control siRNA(NC)and then treated with 40 mg/L tribulus terrestris saponins.MTT assay,wound healing assay,and Transwell assay were used to detect cell proliferation,migration,and invasion,respectively.Western blot was used to detect the protein expression of p21,proliferating nuclear antigen-67(Ki67),epithelial cadherin(E-cadherin),neural cadherin(N-cadherin),Vimentin,Wnt3a,andβ-catenin in the treated cells.RESULTS Compared with the blank control group,the proliferation activity,migration rate,and number of invaded gastric cancer cells in the tribulus terrestris saponins 20 mg/L and 40 mg/L groups were significantly reduced,p21 and E-cadherin protein expression increased,and Ki67,N-cadherin,Vimentin,Wnt3a,andβ-catenin protein expression decreased.Compared with the tribulus terrestris saponins+NC siRNA group,the tribulus terrestris saponins+Wnt3a siRNA group had significantly lower proliferation activity,migration rate,and number of invaded cells,the expression of Wnt3a,β-catenin,Ki67,N-cadherin,and Vimentin decreased,and the expression of p21 and E-cadherin protein increased.CONCLUSION Tribulus terrestris saponins may inhibit the proliferation,migration and invasion of gastric cancer cells by inhibiting the Wnt3a/β-catenin signaling pathway and epithelial-mesenchymal transition.

关 键 词：蒺藜皂苷 Wnt3a/β-catenin信号通路 胃癌细胞 增殖 迁移 侵袭 

分 类 号：R285[医药卫生—中药学]