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二羟基-2,5-苯磺酸盐(多贝斯)可诱导胶质瘤细胞生长停滞并引发凋亡。

Dihydroxy-2,5 benzenesulphonate (dobesilate) elicits growth arrest and apoptosis in glioma cells.

作者信息

Cuevas P, Díaz-González D, Giménez-Gallego G, Dujovny M

机构信息

Departamento de Investigación, Hospital Universitario Ramón y Cajal, Universidad de Alcala de Henares, Madrid, Spain.

出版信息

Neurol Res. 2005 Dec;27(8):797-800. doi: 10.1179/016164105X63665.

DOI:10.1179/016164105X63665
PMID:16354538
Abstract

OBJECTIVES

Dihydroxy-2,5 benzenesulphonate (dobesilate) is used as an oral agent for treatment of vascular complications of diabetic retinopathy. We previously showed that blockade of fibroblast growth factor (FGF) driving angiogenesis with dobesilate inhibited new blood vessel formation in a mouse gelatine plug assay. In the present study we assessed the effects of dobesilate in rat glioma cells.

METHODS

Rat C6 cells line were grown as adherent cells in Dulbecco modified Eagle medium supplemented with 1% (v/v) fetal bovine serum and antibiotics. Calcium dobesilate was added in independent experiments at the following concentrations: 10, 25, 50, 75 and 100 microM, and cells were incubated for 24 hours. Effects of dobesilate in glioma cell proliferation and survival were assessed using crystal violet staining and TUNEL assay, respectively.

RESULTS

Incubation of glioma cells with dobesilate for 24 hours concentration-dependently decreased cell proliferation with an apparent IC50 of 25 microM, and this antiproliferative effect was related to a significant increase in glioma cell apoptosis.

CONCLUSIONS

The results suggest that dobesilate is a promising candidate leading to the development of a new adjuvant therapeutic strategy for gliomas.

摘要

目的

二羟基 - 2,5 - 苯磺酸盐(羟苯磺酸钙)用作治疗糖尿病视网膜病变血管并发症的口服药物。我们之前表明,在小鼠明胶塞试验中,用羟苯磺酸钙阻断驱动血管生成的成纤维细胞生长因子(FGF)可抑制新血管形成。在本研究中,我们评估了羟苯磺酸钙对大鼠胶质瘤细胞的影响。

方法

大鼠C6细胞系在补充有1%(v/v)胎牛血清和抗生素的杜氏改良伊格尔培养基中作为贴壁细胞生长。在独立实验中加入以下浓度的羟苯磺酸钙:10、25、50、75和100微摩尔,细胞孵育24小时。分别使用结晶紫染色和TUNEL检测评估羟苯磺酸钙对胶质瘤细胞增殖和存活的影响。

结果

胶质瘤细胞与羟苯磺酸钙孵育24小时后,细胞增殖呈浓度依赖性降低,表观IC50为25微摩尔,这种抗增殖作用与胶质瘤细胞凋亡显著增加有关。

结论

结果表明,羟苯磺酸钙是一种有前景的候选药物,可用于开发新的胶质瘤辅助治疗策略。

相似文献

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Dihydroxy-2,5 benzenesulphonate (dobesilate) elicits growth arrest and apoptosis in glioma cells.二羟基-2,5-苯磺酸盐(多贝斯)可诱导胶质瘤细胞生长停滞并引发凋亡。
Neurol Res. 2005 Dec;27(8):797-800. doi: 10.1179/016164105X63665.
2
Dobesilate inhibits the activation of signal transducer and activator of transcription 3, and the expression of cyclin D1 and bcl-XL in glioma cells.羟苯磺酸抑制胶质瘤细胞中信号转导子和转录激活子3的激活以及细胞周期蛋白D1和bcl-XL的表达。
Neurol Res. 2006 Mar;28(2):127-30. doi: 10.1179/016164106X97982.
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Antiglioma effects of a new, low molecular mass, inhibitor of fibroblast growth factor.新型低分子质量成纤维细胞生长因子抑制剂的抗神经胶质瘤作用。
Neurosci Lett. 2011 Mar 10;491(1):1-7. doi: 10.1016/j.neulet.2010.12.047. Epub 2010 Dec 28.
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Dobesilate diminishes activation of the mitogen-activated protein kinase ERK1/2 in glioma cells.多贝斯能够减少胶质瘤细胞中丝裂原活化蛋白激酶ERK1/2的激活。
J Cell Mol Med. 2006 Jan-Mar;10(1):225-30. doi: 10.1111/j.1582-4934.2006.tb00303.x.
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Inhibition of choroidal angiogenesis by calcium dobesilate in normal Wistar and diabetic GK rats.
Eur J Pharmacol. 2005 Mar 7;510(1-2):149-56. doi: 10.1016/j.ejphar.2005.01.015.
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[Proliferation inhibition of glioma cells by vitamin K2].维生素K2对胶质瘤细胞的增殖抑制作用
No Shinkei Geka. 1999 Feb;27(2):119-25.
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Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats.汉防己甲素抑制大鼠胶质瘤的肿瘤生长和血管生成。
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Effect of calcium dobesilate and its interaction with aspirin on thrombus formation in vivo.
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Inhibition of tumor growth and prolonged survival of rats with intracranial gliomas following administration of clotrimazole.克霉唑给药后对颅内胶质瘤大鼠肿瘤生长的抑制作用及生存期的延长
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Calcium Dobesilate Prevents Diabetic Kidney Disease by Decreasing Bim and Inhibiting Apoptosis of Renal Proximal Tubular Epithelial Cells.羟苯磺酸钙通过降低Bim和抑制肾近端小管上皮细胞凋亡来预防糖尿病肾病。
DNA Cell Biol. 2017 Apr;36(4):249-255. doi: 10.1089/dna.2016.3276. Epub 2017 Feb 2.

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Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas.信号转导与转录激活因子3:胶质瘤信号通路的分子枢纽
Mol Cancer Res. 2008 May;6(5):675-84. doi: 10.1158/1541-7786.MCR-07-2180.
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Dobesilate diminishes activation of the mitogen-activated protein kinase ERK1/2 in glioma cells.多贝斯能够减少胶质瘤细胞中丝裂原活化蛋白激酶ERK1/2的激活。
J Cell Mol Med. 2006 Jan-Mar;10(1):225-30. doi: 10.1111/j.1582-4934.2006.tb00303.x.