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

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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.