The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
FEBS J. 2010 Feb;277(4):989-99. doi: 10.1111/j.1742-4658.2009.07542.x. Epub 2010 Jan 18.
Previous studies have shown an anticancer effect of vitamin D, but the mechanisms underlying this action have not been fully explored. Here we show that 1,25-dihydroxyvitamin D3 (VD3, the active form of vitamin D) significantly promoted apoptosis in the undifferentiated gastric cancer cell line HGC-27, and this was accompanied by a concurrent increase in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on VD3 treatment. In contrast, knockdown of PTEN expression by stable transfection of PTEN small interfering RNA greatly decreased the apoptosis rate. We further demonstrated that VD3 induced PTEN expression through vitamin D receptor. In addition, our evidence showed that vitamin D receptor, Egr-1 and p300 induced PTEN expression in a synergistic fashion. Furthermore, we found that the histone deacetylase inhibitors trichostatin A and sodium butyrate and the methylation inhibitor 5-aza-2'-deoxycytidine played important roles in vitamin D-induced apoptosis through PTEN upregulation. The data presented in this article suggest potential benefits of vitamin D in gastric cancer therapies in association with the use of trichostatin A/sodium butyrate and 5-aza-2'-deoxycytidine.
先前的研究表明维生素 D 具有抗癌作用，但这种作用的机制尚未完全探索。在这里，我们表明 1,25-二羟维生素 D3（VD3，维生素 D 的活性形式）在未分化的胃癌细胞系 HGC-27 中显著促进细胞凋亡，并且伴随着在 VD3 处理时磷酸酶和张力蛋白同源物缺失的染色体 10（PTEN）表达的同时增加。相比之下，通过稳定转染 PTEN 小干扰 RNA 敲低 PTEN 表达会大大降低细胞凋亡率。我们进一步证明 VD3 通过维生素 D 受体诱导 PTEN 表达。此外，我们的证据表明维生素 D 受体、Egr-1 和 p300 以协同方式诱导 PTEN 表达。此外，我们发现组蛋白去乙酰化酶抑制剂曲古抑菌素 A 和丁酸钠以及甲基化抑制剂 5-氮杂-2'-脱氧胞苷通过上调 PTEN 在维生素 D 诱导的细胞凋亡中发挥重要作用。本文提供的数据表明，维生素 D 与曲古抑菌素 A/丁酸钠和 5-氮杂-2'-脱氧胞苷联合使用，可能对胃癌治疗有益。
