1α,25-Dihydroxyvitamin D3 restrains stem cell-like properties of ovarian cancer cells by enhancing vitamin D receptor and suppressing CD44
1α,25-Dihydroxyvitamin D3 restrains stem cell-like properties of ovarian cancer cells by enhancing vitamin D receptor and suppressing CD44
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1 α,25-二羟基维生素 D3 通过增强维生素 D 受体和抑制 CD44 抑制卵巢癌细胞的干细胞样特性
DOI：
10.3892/or.2019.7116
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发表时间：
2019-06-01
期刊：
影响因子：
4.2
通讯作者：
Li, Bingyan
中科院分区：
文献类型：
--
作者：
Ji, Mintao;Liu, Lizhi;Li, Bingyan
将维生素D与各种癌症类型联系起来的科学证据越来越多，但维生素D对卵巢癌干细胞样细胞（CSC）的影响在很大程度上是未知的。本研究旨在研究维生素D是否能够抑制卵巢癌的干性。在体外和体内，从恶性卵巢表面上皮细胞的侧群（SP）被鉴定为CSC。此外，1 α，25-二羟维生素D-3 [1 α，25（OH）（2）D-3]处理通过降低球体形成率和通过抑制分化簇CD 44、NANOG、OCT 4、SOX 2、Kruppel样因子4和三磷酸腺苷结合盒亚家族G成员2的mRNA表达水平来抑制SP细胞的自我更新能力。此外，1 α，25（OH）（2）D-3处理降低了细胞周期蛋白D1的表达，而增加了β-连环蛋白和维生素D受体（VDR）的表达。值得注意的是，免疫荧光染色证实，1 α，25（OH）（2）D-3促进β-连环蛋白在细胞质中的表达。此外，维生素D-3通过降低体内CD 44和增强β-连环蛋白表达，延迟了由向裸鼠注射卵巢CSC引起的肿瘤形成的发生。总之，1 α，25（OH）（2）D-3通过增强VDR的表达、促进细胞质中β-连环蛋白的表达以及抑制CD 44的表达来抑制卵巢癌细胞的干细胞样性质。这些发现为维生素D在减少癌症CSC的干性方面的功能提供了新的见解。
Scientific evidence linking vitamin D with various cancer types is growing, but the effects of vitamin D on ovarian cancer stem cell-like cells (CSCs) are largely unknown. The present study aimed to examine whether vitamin D was able to restrain the stemness of ovarian cancer. A side population (SP) from malignant ovarian surface epithelial cells was identified as CSCs, in vitro and in vivo. Furthermore, 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] treatment inhibited the self-renewal capacity of SP cells by decreasing the sphere formation rate and by suppressing the mRNA expression levels of cluster of differentiation CD44, NANOG, OCT4, SOX2, Kruppel-like factor 4 and adenosine triphosphate binding cassette subfamily G member 2. Additionally, 1 alpha,25(OH)(2)D-3 treatment decreased the expression of Cyclin D1, whereas it increased the expression of beta-catenin and vitamin D receptor (VDR). Notably, immunofluorescence staining verified that 1 alpha,25(OH)(2)D-3 promoted the expression of beta-catenin in the cytoplasm. Furthermore, vitamin D-3 delayed the onset of tumor formation derived from injection of ovarian CSCs to nude mice, by reducing CD44 and enhancing beta-catenin expressions in vivo. In conclusion, 1 alpha,25(OH)(2)D-3 restrains the stem cell-like properties of ovarian cancer cells by enhancing the expression of VDR, by promoting the expression of beta-catenin in the cytoplasm, and by suppressing the expression of CD44. These findings provide a novel insight into the functions of vitamin D in diminishing the stemness of cancer CSCs.