藏红花素通过调控Smad依赖性信号通路抑制甲状腺未分化癌细胞上皮-间质转化OA
Crocin inhibits epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells by regulating the Smad-dependent signaling pathway
目的:探讨藏红花素对甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)细胞迁移和侵袭能力的影响及其通过Smad依赖性信号通路调节上皮-间质转化(epithelial-mesenchymal transition,EMT)的分子机制.方法:使用不同浓度的藏红花素处理ATC细胞,CCK-8法和流式细胞术分别评估细胞增殖和凋亡;Transwell实验评估藏红花素对ATC细胞迁移和侵袭的影响;蛋白免疫印迹法分析EMT标志物上皮钙黏蛋白(E-cadherin,E-cad)、神经钙黏蛋白(N-cadherin,N-cad)、波形蛋白(vimentin,VIM)、纤连蛋白(fibronectin,FN)和Smad信号通路相关蛋白的表达.构建BHT-101皮下荷瘤模型,评估藏红花素对移植瘤侵袭性的抑制作用;通过免疫组化和蛋白免疫印迹实验,检测基质金属蛋白酶(MMP)-2、MMP-9、N-cad和VIM在肿瘤组织中的表达变化.结果:在40 μmol/L浓度以下,藏红花素处理组较未处理组细胞侵袭和迁移能力显著降低(P＜0.01),E-cad表达上调,N-cad、VIM和FN表达下调;外源性TGF-β干预后,藏红花素对Smad2/3磷酸化的抑制效应得到缓解.体内实验中,藏红花素显著降低BHT-101皮下移植瘤中MMP-2、MMP-9、N-cad和VIM的表达.结论:藏红花素可通过调控Smad依赖性信号传导途径,抑制ATC细胞侵袭和EMT过程.
Objective:To explore the effect of crocin on the migration and invasion ability of anaplastic thyroid carcinoma(ATC)cells and its molecular mechanism of regulating epithelial-mesenchymal transition(EMT)via the Smad-dependent signaling pathway.Methods:ATC cells were treated with different concentrations of crocin.Cell proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry,respectively.The effects of crocin on ATC cell migration and invasion were detected by Transwell assays.Western blotting analysis was used to examine the expression of EMT markers(E-cadherin,N-cadherin,vimentin,fibronectin)and Smad signaling pathway-related proteins.A subcutaneous tumor model was established using BHT-101 cells to evaluate the inhibitory effect of crocin on tumor invasiveness.Immunohistochemistry and Western blotting were performed to detect the expression changes of MMP-2,MMP-9,N-cadherin and vimentin in tumor tissues.Results:At concentrations below 40 μmol/L,crocin treatment significantly reduced cell invasion and migration compared with the untreated group(P＜0.01),accompanied by increased E-cadherin expression and decreased N-cadherin,vimentin and fibronectin expression.The inhibitory effect of crocin on Smad2/3 phosphorylation was alleviated after exogenous TGF-β intervention.In vivo experiments showed that crocin notably downregulated the expression of MMP-2,MMP-9,N-cadherin and vimentin in BHT-101 subcutaneous xenograft tumors.Conclusion:Crocin can inhibit the invasion and EMT of ATC cells by modulating the Smad-dependent signaling pathway.
吴丹;高云;潘兰芬;石磊;李芳;徐松;邓志勇
江苏大学医学院,江苏镇江 212013江苏大学附属昆山医院病理科,江苏苏州 215300江苏大学附属昆山医院病理科,江苏苏州 215300江苏大学附属昆山医院神经外科,江苏苏州 215300江苏大学附属昆山医院科技人才处,江苏苏州 215300江苏大学附属昆山医院病理科,江苏苏州 215300江苏大学附属昆山医院病理科,江苏苏州 215300
医药卫生
甲状腺未分化癌迁移侵袭Smad信号通路藏红花素
anaplastic thyroid carcinoma(ATC)migrationinvasionSmad-dependent signalingcrocin
《江苏大学学报（医学版）》 2026 (1)
44-50,7
国家自然科学基金资助项目(82103288)昆山市级科技专项(KS2204)
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