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多形性胶质母细胞瘤细胞系中辐射增强的血管内皮生长因子(VEGF)分泌——放射抗性的线索?

Radiation-enhanced vascular endothelial growth factor (VEGF) secretion in glioblastoma multiforme cell lines--a clue to radioresistance?

作者信息

Hovinga K E, Stalpers L J A, van Bree C, Donker M, Verhoeff J J C, Rodermond H M, Bosch D A, van Furth W R

机构信息

Department of Radiotherapy, Academic Medical Centre, University of Amsterdam, 1100 DD Amsterdam, The Netherlands.

出版信息

J Neurooncol. 2005 Sep;74(2):99-103. doi: 10.1007/s11060-004-4204-7.

DOI:10.1007/s11060-004-4204-7
PMID:16193379
Abstract

OBJECTIVE

Postoperative radiotherapy is standard treatment for patients with a glioblastoma multiforme (GBM). However, a GBM is radioresistant and almost always recurs, even after a high dose of radiation. A GBM is characterized by its extensive neo-angiogenesis, which can be attributed to the high levels of vascular endothelial growth factor (VEGF). The scope of this study is to investigate the VEGF secretion by GBM cells with different radiosensitivity after irradiation.

METHODS

Three human GBM cell lines (U251, U251-NG2 and U87) were irradiated with single doses of 0, 5, 10 and 20 Gy of gamma-rays from a (137)Cs source. VEGF levels in medium were measured by ELISA at 24, 48 and 72 h after radiation. Cell survival was measured by the XTT assay 7 days after irradiation.

RESULTS

Following single dose radiation, the VEGF levels showed a dose dependent increase in U251, U251-NG2 and U87 glioma cells. Both base-line and radiation-enhanced VEGF levels were about 10-fold higher in U87 compared to U251 and U251-NG2 cells. In addition, in the XTT assay, the U87 was more radioresistant than both U251 and U251-NG2 cell lines (dose modifying factor (DMF) = 1.6 and 1.7 resp).

CONCLUSION

Irradiation enhanced VEGF secretion in all three tested glioma cell lines (up to eight times basal levels). It is tempting to associate the radiation-enhanced VEGF secretion with an increased angiogenic potential of the tumor, which may be a factor in radioresistance.

摘要

目的

术后放疗是多形性胶质母细胞瘤(GBM)患者的标准治疗方法。然而,GBM具有放射抗性,即使在高剂量放疗后几乎总会复发。GBM的特征是广泛的新生血管形成,这可归因于血管内皮生长因子(VEGF)的高水平。本研究的范围是调查照射后不同放射敏感性的GBM细胞的VEGF分泌情况。

方法

三种人GBM细胞系(U251、U251-NG2和U87)用来自(137)Cs源的单剂量0、5、10和20 Gy的γ射线进行照射。放疗后24、48和72小时通过ELISA测量培养基中的VEGF水平。放疗7天后通过XTT试验测量细胞存活率。

结果

单剂量放疗后,U251、U251-NG2和U87胶质瘤细胞中的VEGF水平呈剂量依赖性增加。与U251和U251-NG2细胞相比,U87细胞的基线和放疗增强的VEGF水平均高出约10倍。此外,在XTT试验中,U87比U251和U251-NG2细胞系更具放射抗性(剂量修正因子(DMF)分别为1.6和1.7)。

结论

照射增强了所有三种受试胶质瘤细胞系中的VEGF分泌(高达基础水平的八倍)。很容易将放疗增强的VEGF分泌与肿瘤血管生成潜力增加联系起来,这可能是放射抗性的一个因素。

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