1α,25-二羟维生素D3通过调控TGF-β_(1)诱导的EMT抑制子宫内膜癌细胞的迁移和侵袭  

1α,25-Dihydroxyvitamin D3 Inhibits Migration and Invasion of Endometrial Cancer Cells by Regulating TGF-β_(1)-Induced EMT

作　　者：宋薇 郝津 董自杰[2] 祁洁 SONG Wei;HAO Jin(Shijiazhuang People's Hospital,Hebei Shijiazhuang 050000,China)

机构地区：[1]河北省石家庄市人民医院检验科,河北石家庄050000 [2]河北省石家庄市第三医院检验科,河北石家庄050000

出　　处：《河北医学》2025年第3期425-431,共7页Hebei Medicine

基　　金：河北省卫健委研究课题,(编号:20231602)。

摘　　要：目的:探讨1α,25-二羟维生素D3[1,25(OH)_(2)D_(3)]在子宫内膜癌(EC)中对转化生长因子-β_(1)(TGF-β_(1))诱导的上皮-间充质转化(EMT)的作用。方法:体外培养HEC-1B细胞并用不同浓度的(0、25nM、50nM、100nM、200nM、500nM)1,25(OH)_(2)D_(3)处理,根据CCK-8实验检测细胞活力的结果选用100nM 1,25(OH)_(2)D_(3)进行后续实验。实验分组如下:对照组(Ctrl组)、TGF-β_(1)组、1,25(OH)_(2)D_(3)组、TGF-β_(1)+1,25(OH)_(2)D_(3)组、TGF-β_(1)+TGF-β_(1)抑制剂P144 diammonium组(TGF-β_(1)+P144组),光学显微镜下观察HEC-1B细胞形态变化,Western Blot检测E-cadherin、N-cadherin、Vimentin和TGF-β_(1)蛋白表达,细胞划痕实验检测细胞迁移能力,Transwell实验检测细胞侵袭能力。结果:相比于Ctrl组,TGF-β_(1)组细胞形态由典型的铺路石状变为间质细胞特有的梭形,细胞间排列致密度显著降低,呈现更为疏松的排列模式,同时E-cadherin蛋白表达明显降低(P<0.05),N-cadherin、Vimentin和TGF-β_(1)蛋白表达及迁移距离、侵袭细胞数量明显升高(P<0.05)。相比于Ctrl组,1,25(OH)_(2)D_(3)组E-cadherin蛋白表达明显升高(P<0.05),N-cadherin、Vimentin和TGF-β_(1)蛋白表达及迁移距离、侵袭细胞数量明显降低(P<0.05)。相比于TGF-β_(1)组,TGF-β_(1)+1,25(OH)_(2)D_(3)组和TGF-β_(1)+P144组E-cadherin蛋白表达明显升高(P<0.05),N-cadherin、Vimentin和TGF-β_(1)蛋白表达及迁移距离、侵袭细胞数量明显降低(P<0.05)。结论:1,25(OH)_(2)D_(3)能够通过调控TGF-β_(1)诱导的EMT来抑制HEC-1B细胞的迁移和侵袭。Objective:To explore the role of 1α,25-dihydroxyvitamin D3[1,25(OH)_(2)D_(3)]in the regulation of epithelial-mesenchymal transition(EMT)induced by transforming growth factor-β_(1)(TGF-β_(1))in endometrial cancer(EC).Methods:HEC-1B cells were cultured in vitro and treated with different concentrations(0,25 nM,50 nM,100 nM,200 nM,500 nM)of 1,25(OH)_(2)D_(3).Based on the results of the CCK-8 assay to assess cell viability,100 nM 1,25(OH)_(2)D_(3) was selected for subsequent experiments.The experimental groups were as follows:control group(Ctrl),TGF-β_(1)group,1,25(OH)_(2)D_(3) group,TGF-β_(1)+1,25(OH)_(2)D_(3) group,TGF-β_(1)+TGF-β_(1)inhibitor P144 diammonium group(TGF-β_(1)+P144).Cell morphological changes were observed under an optical microscope,and Western blotting was used to detect the protein expression of E-cadherin,N-cadherin,Vimentin,and TGF-β_(1).The migration ability of the cells was assessed by the scratch assay,and the invasion ability was assessed by the Transwell assay.Results:Compared with the Ctrl group,cells in the TGF-β_(1)group changed from typical cobblestone-like morphology to spindle-shaped mesenchymal cell morphology,with significantly reduced cell-cell adhesion and a more dispersed arrangement.Meanwhile,E-cadherin expression was significantly reduced(P<0.05),and the expression of N-cadherin,Vimentin,and TGF-β_(1),as well as migration distance and invasion cell count,were significantly increased(P<0.05).Compared with the Ctrl group,the 1,25(OH)_(2)D_(3) group showed significantly higher E-cadherin expression(P<0.05),and significantly lower expression of N-cadherin,Vimentin,and TGF-β_(1),as well as migration distance and invasion cell count(P<0.05).Compared with the TGF-β_(1)group,both the TGF-β_(1)+1,25(OH)_(2)D_(3) group and the TGF-β_(1)+P144 group exhibited significantly higher E-cadherin expression(P<0.05),and significantly lower expression of N-cadherin,Vimentin,and TGF-β_(1),as well as migration distance and invasion cell count(P<0.05).Conclusion:1,25(OH)_(2)D_(3) can

关 键 词：1α 25-二羟维生素D3 TGF-β_(1) 上皮-间充质转化 子宫内膜癌 迁移 侵袭 

分 类 号：R73[医药卫生—肿瘤]