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维生素 D 类似物他卡西醇和卡泊三醇抑制 T98G 人胶质母细胞瘤细胞的增殖和迁移。

Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and Migration of T98G Human Glioblastoma Cells.

机构信息

Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

出版信息

Basic Clin Pharmacol Toxicol. 2018 Aug;123(2):130-136. doi: 10.1111/bcpt.13007. Epub 2018 Apr 25.

DOI:10.1111/bcpt.13007
PMID:29575677
Abstract

The active form of vitamin D (1α,25-dihydroxyvitamin D) acts as a steroid hormone and binds to the vitamin D receptor. This receptor is expressed in most cell types including cells in the central nervous system (CNS). Vitamin D has several functions in the body including effects on brain development, neuroprotection and immunological regulation. It has been shown that vitamin D has antiproliferative activities in different cancer cell lines. Tacalcitol and calcipotriol are synthetic analogues of 1α,25-dihydroxyvitamin D with reduced effect on calcium metabolism. The aim of this study was to analyse the effects of tacalcitol and calcipotriol on cell viability, proliferation and migration in the human glioblastoma cell line T98G. Glioblastoma is the most lethal type of primary tumours in the CNS. Both analogues decreased cell viability and/or growth, dose-dependently, in concentrations between 1 nM and 10 μM. Manual counting indicated suppressive effects by the vitamin D analogues on proliferation. Treatment with tacalcitol strongly suppressed thymidine incorporation, indicating that the vitamin D analogues mainly inhibit proliferation. Also, effects on cell migration were measured with wound-healing assay. Both calcipotriol and tacalcitol reduced the migration rate of T98G cells compared to vehicle-treated cells. However, they had no effect on caspase-3 and -7 activities, suggesting that their mechanism of action does not involve induction of apoptosis. The current results indicate that the vitamin D analogues tacalcitol and calcipotriol strongly reduce proliferation and migration of human glioblastoma T98G cells, suggesting a potential role for this type of compounds in treatment of brain cancer.

摘要

活性形式的维生素 D(1α,25-二羟维生素 D)作为一种类固醇激素,与维生素 D 受体结合。该受体在包括中枢神经系统(CNS)细胞在内的大多数细胞类型中表达。维生素 D 在体内具有多种功能,包括对大脑发育、神经保护和免疫调节的影响。已经表明,维生素 D 在不同的癌细胞系中具有抗增殖活性。他卡西醇和卡泊三醇是 1α,25-二羟维生素 D 的合成类似物,对钙代谢的影响较小。本研究的目的是分析他卡西醇和卡泊三醇对人胶质母细胞瘤细胞系 T98G 细胞活力、增殖和迁移的影响。胶质母细胞瘤是中枢神经系统中最致命的原发性肿瘤类型。两种类似物在 1 nM 至 10 μM 的浓度范围内均呈剂量依赖性降低细胞活力和/或生长。手动计数表明维生素 D 类似物对增殖具有抑制作用。他卡西醇处理强烈抑制胸苷掺入,表明维生素 D 类似物主要抑制增殖。还使用划痕愈合试验测量了对细胞迁移的影响。与用载体处理的细胞相比,卡泊三醇和他卡西醇均降低了 T98G 细胞的迁移率。然而,它们对 caspase-3 和 caspase-7 的活性没有影响,表明它们的作用机制不涉及诱导细胞凋亡。目前的结果表明,维生素 D 类似物他卡西醇和卡泊三醇强烈抑制人胶质母细胞瘤 T98G 细胞的增殖和迁移,表明此类化合物在治疗脑癌方面具有潜在作用。

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