Development of chemotherapy according to induction of DNA Topoisomerase activity.

根据 DNA 拓扑异构酶活性的诱导开发化疗。

• 批准号: 07671325
• 负责人: ANZAI Haruyuki
• 金额: $ 0.51万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671325/
• 关键词: DNA TOPOISOMERASE; TOPOTECAN; ETOPOSIDE; トポイソメラーゼI; トポイソメラーゼII; 化学療法; トポテカン; エトポシド; 大腸癌; トポイソメラーゼ; Topotecan.(トポテカン); Etoposide(エトポシド)

Topoisomerase (Topo) I and II activities against each cell line were related to ED50 of Topo I and II inhibitor. The cell line which indicated. high activity of Topo is very sensitive to Topo inhibitor as the target of this enzyme.Sequential administration of Topo I and II inhibitor revealed more synergistic effect compared to simultaneous administration of these inhibitor. In addition, the precedent administration of ED10 Topo inhibitor increase the cytocidal effect of complementary Topo inhibitor synergistically. Especially, this phenomenon was observed in the cell line which showed high activity of Topo I when Topo I inhibitor were exposed precedentally.The induction of Topo enzyme activity were studied due to Topo I and II inhibitor. But this phenomenon could not observed although Topo enzyme activity at 2,4,8,12,24 hr after the exposure of ED10,50 Topo inhibitor were measured.Optimal dose and schedule for the induction of Topo enzyme activity could not find out in vivo condition, neither.Therefore, although induction of Topo enzyme activity could not detected we concluded that measurement of Topo I and II enzyme activity, and following administration of Topo inhibitor against higher Topo activity of the cancer cell and precedent administration of Topo inhibitor against weak enzyme activity must be important in the clinical apply for the colon cancer chemotherapy.

拓扑异构酶(Topo)I、II对各细胞株的杀伤活性与Topo I、II抑制剂的ED50有关。该细胞系表明。TOPO的高活性对作为该酶靶标的TOPO抑制剂非常敏感，与同时使用这两种抑制剂相比，顺序使用TOPO I和II抑制剂显示出更多的协同作用。此外，预先给予ED10 TOPO抑制剂可协同增强互补TOPO抑制剂的细胞杀伤作用。特别是在TOPO I高活性的细胞系中，当TOPO I抑制剂预先暴露时，可以观察到这种现象。但在ED10、50、TOPO抑制剂作用后2、4、8、12、24小时检测Topo酶活性，未观察到这一现象。TOPO酶活性诱导的最佳剂量和程序在体内也找不到。因此，虽然未能检测到Topo酶活性的诱导，但我们认为，检测Topo I、II酶活性，以及在给予Topo抑制剂后针对癌细胞Topo活性升高以及先行Topo抑制剂针对弱酶活性应用在结肠癌化疗中具有重要的临床意义。