INNOVATION FOR TISSUE-SPECIFIC RADIO-SENCITIZATION OF SELECTIVE INHIBITOR OF CYCLO-OXYGENASE 2 (COX-2)

一个众所周知的事实是，活跃复制的肿瘤细胞和分化的无复制活性的神经元在放射敏感性上存在很大差异。本研究以环氧合酶-2(COX-2)抑制剂和羧基肽酶B(HBCPB)为研究对象，探讨了COX-2和HBCPB在细胞凋亡诱导中的作用。COX-2研究：以人血管肉瘤细胞株(ISO-HAS)为研究对象，研究了照射和选择性COX-2抑制剂NS-389联合应用对肿瘤生长和血管生成的影响。COX-2效应与血管内皮生长因子蛋白表达的关系NS-389呈剂量依赖性地降低细胞存活率，照射后VEGF-蛋白表达也呈剂量依赖性增加，联合使用NS-398可抑制这一作用。由此可见，NS-389与辐射具有共用效应，其细胞生长抑制作用与VEGF有关。HBCPB研究：以大鼠海马神经元原代培养体系为研究对象，以非复制细胞为典型例子。在该系统中，我们分析了β-淀粉样蛋白1-42低聚物的神经毒性及其被人脑羧基肽酶B(HBCPB)解离后的细胞凋亡诱导作用，结果表明该系统对COX-2前列腺素谱系无影响，提示该系统是选择性细胞死亡以维持内环境稳定的独立调节系统。

It is a well-known fact that there iis a great difference in radiosensitivity between actively replicating tumor cell and differentiated neurons without replicating activity. In this research project, we focused on cyclo-oxygenase 2 (COX-2) inhibitors, whose inhibitory action of cell replication is recognized in many tumor cell linse, and carboxypeptidase B (HBCPB) which exhibits inhibitory activity for cell toxicity be dissociation of beta-amyloid oligomer, and snslyzed their functions with regard to apoptosis induction.COX-2 study : Using human hemangiosarcoma cell line (ISO-HAS), following analyses were performed.Effects in tumor growth and angiogenesis by co-usage of irradiation and NS-389, a selective COX-2 inhibitor.Relationship of COX-2 effect and VEGF protein expression.As for results, cell viability was decreased by NS-389 in a dose dependent fashion, and the VEGF-protein expression was increased by irradiation also in a dose-dependent manner, which was inhibited by co-usage of NS-398. Therefore, it seems that NS-389 has a co-usage effect with irradiation, and its cell growth inhibitory effect is relevant to VEGF.HBCPB study : As a typical example of non-replicating cell, using rat hippocampus primary neuron culture system was used. In this system, neuro-toxicity of beta-amyloid 1-42 oligomer, and its dissociation by human brain carboxypeptidase B (HBCPB) were analyzed especially with respect to apoptosis induction.As a result, this system induced no effects in the COX-2 prostaglandin lineage, and suggests that these are independent regulation system for selective cell death to keep homeostasis.