CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid cancer cells.
CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid cancer cells.
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DOI：
10.3892/etm.2018.6536
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发表时间：
2018-10
影响因子：
2.7
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Hu N;Zhang H
25-羟基维生素D3 -24-羟化酶（CYP 24 A1）是中和维生素D活性的关键酶，可能具有抗肿瘤作用。因此，本研究的目的是探索维生素D的活性代谢产物1，25-二羟维生素D（1，25-D3）在CYP 24 A1下调后对甲状腺癌细胞的影响。Cell Counting Kit-8检测发现，CYP 24 A1敲低增强了1，25-D3对甲状腺癌细胞的抗增殖作用。此外，划痕和Transwell实验结果表明，CYP 24 A1敲低增强了1，25-D3对细胞迁移的抑制作用。逆转录定量聚合酶链反应和蛋白质印迹分析结果表明，1，25-D3和CYP 24 A1敲低处理协同增强上皮相关基因E-cadherin的表达，降低间质相关基因N-cadherin和vimentin的表达。与25-D3单独治疗组相比，CYP 24 A1敲低和1，25-D3治疗后，基质金属蛋白酶2和金属蛋白酶抑制剂1的表达分别显著降低和升高。此外，与单独接受1，25-D3治疗的组相比，这种协同作用显著降低了蛋白激酶B（Akt）和β-连环蛋白活性。本研究的结果表明，CYP 24 A1敲低有助于1，25-D3的抗肿瘤作用，这种作用可能是由于Akt和β-catenin信号通路的失活。因此，CYP 24 A1敲低和1，25-D3治疗可协同用作治疗甲状腺癌患者的新治疗策略。
It has been demonstrated that 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1) is a key enzyme that neutralizes vitamin D activity, which may have an anti-tumor effect. Therefore, the aim of the current study was to explore the effect of the active metabolite of vitamin D, 1,25-dihydroxyvitamin D (1,25-D3) on thyroid cancer cells following the downregulation of CYP24A1. A Cell Counting Kit-8 assay identified that CYP24A1 knockdown enhanced the anti-proliferative effects of 1,25-D3 on thyroid cancer cells. Furthermore, the results of the scratch wound and Transwell assays indicated that CYP24A1 knockdown enhanced the inhibitory effect of 1,25-D3 on cell migration. The results from reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that treatment with 1,25-D3 and CYP24A1 knockdown synergistically enhanced the expression of the epithelial-related gene E-cadherin and decreased the expression of the mesenchymal-related genes N-cadherin and vimentin. Following CYP24A1 knockdown and treatment with 1,25-D3, the expression of matrix metalloproteinase 2 and metalloproteinase inhibitor 1 were significantly decreased and increased, respectively, compared with the group that underwent treatment with 25-D3 alone. Furthermore, protein kinase B (Akt) and β-catenin activity was significantly decreased by this synergetic effect compared with the group that underwent treatment with 1,25-D3 alone. The results of the current study suggest that CYP24A1 knockdown contributes to the anti-tumor effect of 1,25-D3 and that this effect may be due to deactivation of the Akt and β-catenin signaling pathways. Therefore, CYP24A1 knockdown and 1,25-D3 treatment may be used synergistically as a novel therapeutic strategy to treat patients with thyroid cancer.
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