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芒果苷通过诱导微小RNA-15b和抑制基质金属蛋白酶-9的表达来调节胶质瘤细胞的增殖和凋亡。

Mangiferin regulates proliferation and apoptosis in glioma cells by induction of microRNA-15b and inhibition of MMP-9 expression.

作者信息

Xiao Jinsong, Liu Li, Zhong Zian, Xiao Cheng, Zhang Junjian

机构信息

Division of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.

出版信息

Oncol Rep. 2015 Jun;33(6):2815-20. doi: 10.3892/or.2015.3919. Epub 2015 Apr 21.

Abstract

Mangiferin, a flavonoid extracted from the leaves of the Anacardiaceae plant, the mango tree, has physiological activity and pharmacological effects in many aspects. The present study aimed to clarify the effect of mangiferin on proliferation and apoptosis of glioma cells and the mechanism of these curative effects of mangiferin. In this experiment, we detected the proliferation using 3-(4,5-dimethylthylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Then, cell apoptosis of U87 glioma cells was measured with the Annexin V-FITC/propidium iodide (PI) apoptosis detection kit, DAPI staining assay and the caspase-3 and caspase-9 activity assay kit. Next, quantitative real-time PCR and gelatin zymography were used to analyze the expression of microRNA-15b (miR-15b) and matrix metalloproteinase-9 (MMP-9), respectively. MMP-9 agonist, miR-15b mimics and anti-miR-15b mimics were added to the U87 glioma cells for elucidating the mechanisms involved in the curative effects of mangiferin. In the present study, mangiferin notably restrained the proliferation and increased the apoptosis of the U87 glioma cells. Meanwhile, mangiferin specifically promoted the expression of miR-15b and suppressed the level of MMP-9 in the U87 glioma cells. miR-15b regulated the expression of MMP-9 in the U87 glioma cells. MMP-9 agonist and anti-miR‑15b reduced the curative effects of mangiferin in the U87 glioma cells. In summary, mangiferin regulates proliferation and apoptosis in glioma cells by induction of miR-15b and inhibition of MMP-9 expression.

摘要

芒果苷是从漆树科植物芒果树的叶子中提取的一种黄酮类化合物,在许多方面具有生理活性和药理作用。本研究旨在阐明芒果苷对胶质瘤细胞增殖和凋亡的影响以及这些治疗作用的机制。在本实验中,我们使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法检测增殖情况。然后,用膜联蛋白V-异硫氰酸荧光素/碘化丙啶(PI)凋亡检测试剂盒、4',6-二脒基-2-苯基吲哚(DAPI)染色法和半胱天冬酶-3和半胱天冬酶-9活性检测试剂盒检测U87胶质瘤细胞的凋亡情况。接下来,分别使用定量实时聚合酶链反应(qRT-PCR)和明胶酶谱法分析微小RNA-15b(miR-15b)和基质金属蛋白酶-9(MMP-9)的表达。将MMP-9激动剂、miR-15b模拟物和抗miR-15b模拟物添加到U87胶质瘤细胞中,以阐明芒果苷治疗作用的相关机制。在本研究中,芒果苷显著抑制U87胶质瘤细胞的增殖并增加其凋亡。同时,芒果苷特异性促进U87胶质瘤细胞中miR-15b的表达并抑制MMP-9的水平。miR-15b调节U87胶质瘤细胞中MMP-9的表达。MMP-9激动剂和抗miR-15b降低了芒果苷对U87胶质瘤细胞的治疗效果。综上所述,芒果苷通过诱导miR-15b和抑制MMP-9表达来调节胶质瘤细胞的增殖和凋亡。

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