1α,25-二羟维生素D3通过调控TGF-β<sub>1</sub>诱导的EMT抑制子宫内膜癌细胞的迁移和侵袭

doi:10.3969/j.issn.1006-6233.2025.03.013

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摘要 目的: 探讨1α,25-二羟维生素D3[1,25(OH)₂D₃]在子宫内膜癌(EC)中对转化生长因子-β₁(TGF-β₁)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)₂D₃处理,根据CCK-8实验检测细胞活力的结果选用100nM 1,25(OH)₂D₃进行后续实验。实验分组如下:对照组(Ctrl组)、TGF-β₁组、1,25(OH)₂D₃组、TGF-β₁+1,25(OH)₂D₃组、TGF-β₁+TGF-β₁抑制剂P144　diammonium组(TGF-β₁+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-β₁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-β₁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-β₁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)₂D₃组E-cadherin蛋白表达明显升高(P<0.05),N-cadherin、Vimentin和TGF-β₁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-β₁组,TGF-β₁+1,25(OH)₂D₃组和TGF-β₁+P144组E-cadherin蛋白表达明显升高(P<0.05),N-cadherin、Vimentin和TGF-β₁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)₂D₃能够通过调控TGF-β₁诱导的EMT来抑制HEC-1B细胞的迁移和侵袭。

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关键词 ： 1α,25-二羟维生素D3, TGF-β₁, 上皮-间充质转化, 子宫内膜癌, 迁移, 侵袭

Abstract：Objective: To explore the role of 1α,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] in the regulation of epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β₁ (TGF-β₁) 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)₂D₃. Based on the results of the CCK-8 assay to assess cell viability, 100 nM 1,25(OH)₂D₃ was selected for subsequent experiments. The experimental groups were as follows: control group (Ctrl), TGF-β₁ group, 1,25(OH)₂D₃ group, TGF-β₁ + 1,25(OH)₂D₃ group, TGF-β₁ + TGF-β₁ inhibitor P144 diammonium group (TGF-β₁ + 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-β₁. 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-β₁ 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-β₁, as well as migration distance and invasion cell count, were significantly increased (P<0.05). Compared with the Ctrl group, the 1,25(OH)₂D₃ group showed significantly higher E-cadherin expression (P<0.05), and significantly lower expression of N-cadherin, Vimentin, and TGF-β₁, as well as migration distance and invasion cell count (P<0.05). Compared with the TGF-β₁ group, both the TGF-β₁ + 1,25(OH)₂D₃ group and the TGF-β₁ + P144 group exhibited significantly higher E-cadherin expression (P<0.05), and significantly lower expression of N-cadherin, Vimentin, and TGF-β₁, as well as migration distance and invasion cell count (P<0.05). Conclusion: 1,25(OH)₂D₃ can inhibit the migration and invasion of HEC-1B cells by regulating TGF-β₁-induced EMT.

Key words： 1α,25-Dihydroxyvitamin D3 TGF-β₁ Epithelial-mesenchymal transition (EMT) Endometrial cancer Migration Invasion

基金资助:河北省卫健委研究课题,(编号:20231602)

引用本文:

宋薇, 郝津, 董自杰, 祁洁. 1α,25-二羟维生素D3通过调控TGF-β₁诱导的EMT抑制子宫内膜癌细胞的迁移和侵袭[J]. 河北医学, 2025, 31(3): 425-430.
SONG Wei, HAO Jin, et al. 1α,25-Dihydroxyvitamin D3 Inhibits Migration and Invasion of Endometrial Cancer Cells by Regulating TGF-β₁-Induced EMT. HeBei Med, 2025, 31(3): 425-430.

链接本文:

http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.03.013 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I3/425

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