All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro
All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro
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DOI：
10.3892/ol.2015.3120
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发表时间：
2015-06-01
期刊：
影响因子：
2.9
通讯作者：
Guo, Shiwen
中科院分区：
文献类型：
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作者：
Liang, Chen;Yang, Ling;Guo, Shiwen
全反式维甲酸（ATRA）是维生素A的衍生物，可诱导胶质瘤细胞分化和凋亡，并抑制其增殖。然而，全反式维甲酸对胶质瘤的迁移和侵袭的影响仍然知之甚少。此外，虽然普遍认为ATRA可以诱导胶质瘤细胞凋亡并抑制其增殖，但ATRA的浓度与作用之间的关系尚不清楚。因此，本研究探讨了ATRA对胶质瘤细胞迁移、侵袭、凋亡和增殖的影响。用不同浓度的ATRA（0、5、10、20和40 μ mol/l）处理U87和SHG 44胶质瘤细胞系。划痕伤口愈合测定和基质胶侵袭测定分别用于研究细胞迁移和侵袭。流式细胞仪检测细胞凋亡和细胞周期分布。采用逆转录-定量聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blotting）检测各组细胞基质金属蛋白酶（MMP）-2和-9的表达。与空白对照组相比，ATRA处理后胶质瘤细胞的迁移、侵袭和增殖均受到明显抑制，凋亡率明显增加。此外，剂量-效应关系之间确定了每一个效果和ATRA治疗。低浓度ATRA（5 μ mol/l和10 μ mol/l）对U87胶质瘤细胞MMP-2 mRNA和蛋白表达无明显影响（P>0.05）。然而，治疗与高浓度的ATRA，包括20和40 μ mol/l的ATRA，显着下调MMP-2在U87细胞的表达水平。与U87细胞相比，ATRA处理SHG 44细胞后MMP-2 mRNA和蛋白表达明显下调，且呈剂量依赖性（P
All-trans retinoic acid (ATRA) is a derivative of vitamin A that can induce differentiation and apoptosis, as well as inhibit proliferation, in glioma cells. However, the effect of ATRA on the migration and invasiveness of glioma remains poorly understood. In addition, although it is universally accepted that ATRA can induce apoptosis and inhibit proliferation in glioma cells, the association between the concentration and effects of ATRA remain unclear. Therefore, the present study investigated the effects of ATRA treatment on the migration, invasion, apoptosis and proliferation of glioma cells. The U87 and SHG44 glioma cell lines were treated with various concentrations of ATRA, consisting of 0, 5, 10, 20 and 40 mu mol/l. A scratch wound healing assay and a Matrigel invasion assay were used to investigate cell migration and invasion, respectively. Flow cytometry was performed to investigate apoptosis and cell cycle distribution. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to investigate the expression of matrix metalloproteinase (MMP)-2 and -9 in each cell treatment group. Following treatment with ATRA, the migration, invasion and proliferation of the glioma cells were significantly inhibited, and the apoptosis rate was significantly increased compared with that of the blank control group. Furthermore, a dose-effect association was identified between each effects and ATRA treatment. The mRNA and protein expression of MMP-2 in U87 glioma cells was not significantly affected following treatment with low concentrations of ATRA, consisting of 5 and 10 mu mol/l ATRA, compared with the expression in the control group (P>0.05). However, treatment with high concentrations of ATRA, consisting of 20 and 40 mu mol/l ATRA, significantly downregulated the expression levels of MMP-2 in U87 cells. In contrast to U87 cells, the administration of ATRA treatment to SHG44 glioma cells resulted in a significant and dose-dependent downregulation in MMP-2 mRNA and protein expression (P