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抑制 HO-1 增强 As2O3 对胶质瘤疗效的实验研究

抑制 HO-1 增强 As2O3 对胶质瘤疗效的实验研究. 刘耀华 陈晓丰 梁元 郑秉杰 赵世光. 哈尔滨医科大学附属第一医院 神经外科. It was proved that subarachnoid injection of As 2 O 3 is safe. Intraoperative transplantation of Ommaya device (ACNU or ACNU+As 2 O 3 ). Preoperation. 47 male, Grade Ⅲ-Ⅳ ：

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抑制 HO-1 增强 As2O3 对胶质瘤疗效的实验研究

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  1. 抑制HO-1增强As2O3对胶质瘤疗效的实验研究 刘耀华 陈晓丰 梁元 郑秉杰 赵世光 哈尔滨医科大学附属第一医院 神经外科

  2. It was proved that subarachnoid injection of As2O3 is safe.

  3. Intraoperative transplantation of Ommaya device (ACNU or ACNU+As2O3)

  4. Preoperation 47 male, Grade Ⅲ-Ⅳ： Ommaya device (ACNU+As2O3), Arterial chemotherapy (As2O3), and Radiotherapy One year after operation

  5. Recurrent glioma 54 female, Grade Ⅲ: Ommaya device (ACNU+As2O3), Arterial chemotherapy (As2O3), and Radiotherapy 6 months after the second operation

  6. Preoperation 47 female, Grade Ⅲ-Ⅳ: Ommaya device (ACNU+As2O3), Arterial chemotherapy (As2O3), and Radiotherapy 2 years after operation

  7. 44 male, Grade Ⅲ: Ommaya device (ACNU+As2O3), Arterial chemotherapy (As2O3), and Radiotherapy Case3 MRI before operation Before operative MRI CT one week after operative and the first chemotherapy Preoperative CT CT one and half a year after operation

  8. 研究背景 三氧化二砷（As2O3）与肿瘤治疗 • 国内外研究发现As2O3在实体肿瘤治疗受到限制，小剂量药物不能达到治疗效果，而增大剂量往往增加药物毒性； • As2O3作用于细胞后不仅引起细胞毒性效应，同时还激活细胞内一些保护性分子和信号通路； • As2O3诱导细胞凋亡的机制被认为主要是通过活性氧（ROS）的诱导而实现； • ROS可以诱导细胞保护性分子血红素加氧酶-1(HO-1); • HO-1在胶质瘤中广泛表达； • 抑制HO-1是否可以提高As2O3对胶质瘤的治疗效果？

  9. 实验设计 • 胶质瘤细胞系U251MG用As2O3处理，检测细胞活性、线粒体膜电位（MMP），并观察ROS清除剂LNAC对细胞是否有保护作用； • 检测As2O3诱导胶质瘤细胞ROS生成、MAPK信号通路的活化，HO-1的诱导以及LNAC对其影响； • 使用HO-1的诱导剂和抑制剂处理细胞，观察其对As2O3效应的影响； • Nrf2是HO-1表达的重要转录因子，SiRNA技术干扰Nrf2表达后对比细胞对As2O3的敏感性。

  10. Cell Viability ** P<0.01 compared with control; ▼P<0.01 compared with LNAC untreated cells.

  11. Mitochondrial Membrane Potential

  12. Sub-G1 (PI Staining)

  13. ROS induction

  14. Downstreams of ROS

  15. Nrf2 Translocation

  16. Effects of HO-1 inducer * P<0.01

  17. Effects of HO-1 inducer * P<0.01

  18. Effects of HO-1 inhibitor * P<0.01 * P<0.01

  19. Knockdown of Nrf2 ATO (5uM) Random Nrf2 Random Nrf2 0h 3h 6h 0h 3h 6h HO-1 Nrf2 b-actin GAPDH

  20. Knockdown of Nrf2 * P<0.01

  21. Knockdown of Nrf2

  22. Knockdown of Nrf2 * P<0.01

  23. Cell death ROS Nrf2 activation ATO HO-1 induction

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