Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells
Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells
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DOI：
10.1007/s11060-007-9385-4
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发表时间：
2007-10-01
影响因子：
3.9
通讯作者：
Sminia, Peter
中科院分区：
文献类型：
--
作者：
Bijnsdorp, Irene V.;van den Berg, Jaap;Sminia, Peter
考克斯-2蛋白在人类恶性胶质瘤中经常过表达。这种表达与其侵袭性生长特征和患者预后不良有关。靶向考克斯-2通路可能会改善胶质瘤的治疗。在这项研究中，选择性考克斯-2抑制剂美洛昔康单独和联合辐射的影响，在体外人胶质瘤细胞进行了研究。在实验中使用一组三种神经胶质瘤细胞系（D384、U87和U251），其中U87细胞表达组成型考克斯-2。通过克隆形成试验测定对美洛昔康和辐射（剂量范围为0-6戈伊）的反应，通过生长分析评价细胞增殖，通过流式细胞仪评价细胞周期分布。暴露于250-750 μ M美洛昔康24-72 h导致时间和剂量依赖性生长抑制，24 h后几乎完全抑制所有细胞系。暴露于750 μ M美洛昔康24小时，D384（18-27%）和U251（17-41%）细胞中处于放射敏感性G（2）/M细胞周期期的细胞比例增加。750 μ M美洛昔康导致D384（DMF：2.19）和U87（DMF：1.25）细胞的放射增敏，但不导致U251细胞（DMF：1.08）的放射增敏。选择性考克斯-2抑制剂美洛昔康对人脑胶质瘤细胞具有考克斯-2非依赖性生长抑制和放射增敏作用。
The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated on human glioma cells in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the experiments from which U87 cells expressed constitutive COX-2. The response to meloxicam and irradiation (dose-range of 0-6 Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24-72 h exposure to 250-750 mu M meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24 h for all cell lines. Exposure to 750 mu M meloxicam for 24 h increased the fraction of cells in the radiosensitive G(2)/M cell cycle phase in D384 (18-27%) and U251 (17-41%) cells. 750 mu M meloxicam resulted in radiosensitization of D384 (DMF:2.19) and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent growth inhibition and radiosensitization of human glioma cells.