摘要
目的本研究旨在探讨丹酚酸B(salvianolicacid B,Sal B)对小鼠肝癌细胞Hepa1-6是否有抑制作用,并深入探讨是否通过TGF-β1/Smad2信号通路发挥作用。方法体外实验将Hepa1-6细胞分为对照组、TGF-β1刺激组、TGF-β1+Sal B组,检测细胞增殖、迁移及pSmad2C、pSmad2L蛋白表达。体内实验构建Hepa1-6荷瘤C57小鼠模型,随机分为模型组、Sal B(7.5、15、30 mg·kg^(-1)·d^(-1))组和秋水仙碱组(0.1 mg·kg^(-1)·d^(-1)),每组8只。干预4周,测量肿瘤体积,采用HE染色和Western blot检测组织病理及pSmad2C、pSmad2L、Smad2蛋白表达。结果体外实验表明,Sal B能有效抑制TGF-β1诱导的Hepa1-6细胞增殖与迁移,并降低pSmad2C、pSmad2L蛋白表达。体内实验显示,Sal B可剂量依赖性地抑制肿瘤生长,且Western blot结果证实其能下调瘤组织中pSmad2C、pSmad2L蛋白水平。结论Sal B对TGF-β1刺激后的Hepa1-6细胞生长具有明显的抑制作用,其机制可能与激活TGF-β1/Smad2信号通路密切相关。此外,Sal B在体内对TGF-β1诱导的荷瘤生长的抑制作用可能是通过激活TGFβ1/Smad2信号通路实现的。
Aim To investigate the inhibitory effect of salvianolicacid B(Sal B)on mouse hepatocellular carcinoma cells(Hepa1-6)and to explore its role through the TGF-β1/Smad2 signaling pathway.Methods Hepa1-6 cells were divided into the control group,TGF-β1 stimulation group,and TGF-β1+Sal B group.Cell proliferation and migration ability were assessed.PSmad2C,pSmad2L expression levels,pSmad2C,pSmad2L and Smad2 protein changes were detected using cellular immunofluorescence.Tumorigenic mice were randomly divided into the model group,Sal B(7.5 mg·kg^(-1)·d^(-1))group,Sal B(15 mg·kg^(-1)·d^(-1))group,Sal B(30 mg·kg^(-1)·d^(-1))group,and colchicine group(0.1 mg·kg^(-1)·d^(-1)),with 8 mice in each group.Body weight,tumor volume changes,tumor histopathology,pSmad2C,pSmad2L protein changes were all detected.Results Sal B effectively inhibited the TGF-β1induced proliferation and migration of Hepa1-6 cells,concomitantly reducing the protein expression levels of pSmad2C and pSmad2L.In vivo,Sal B potently suppressed tumor growth in a xenograft model in a dose-dependent manner.Histopathological(HE)staining and Western blot analysis further confirmed that Sal B treatment inhibited tumor growth and downregulated the protein expression of pSmad2C and pSmad2L in tumor tissues.Conclusions Sal B exhibits a significant inhibitory effect on the growth of Hepa1-6 cells stimulated by TGF-β1,and this mechanism may be closely associated with the activation of the TGF-β1/Smad2 signaling pathway.Furthermore,the inhibitory effect of Sal B on TGF-β1-induced tumor growth in vivo is likely mediated through the activation of the TGF-β1/Smad2 signaling pathway.
作者
刘文博
孙良捷
邓洁
贾心璐
杨雁
LIU Wen-bo;SUN Liang-jie;DENG Jie;JIA Xin-lu;YANG Yan(School of Pharmaceutical Sciences,Anhui Medical University,Hefei 230032,China;The Second Clinical Medical College,Anhui Medical University,Hefei 230032,China)
出处
《中国药理学通报》
北大核心
2026年第2期296-304,共9页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 82374084)
国家级大学生创新训练计划项目(No 202310366026)
临床医学“5+3”一体化专业(含儿科学方向)"早期接触科研"训练计划项目(No 2022-ZQKY-175,2023-ZQKY-144)。