SU5416 和 EGCG 协同作用，抑制血管生成和生存因子，并诱导细胞周期停滞，促进人恶性神经母细胞瘤 SH-SY5Y 和 SK-N-BE2 细胞凋亡。
SU5416 and EGCG work synergistically and inhibit angiogenic and survival factors and induce cell cycle arrest to promote apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells.
机构信息
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, 29209, USA.
出版信息
Neurochem Res. 2011 Aug;36(8):1383-96. doi: 10.1007/s11064-011-0463-9. Epub 2011 Apr 7.
Abstract
Malignant neuroblastomas are solid tumors in children. Available therapeutic agents are not highly effective for treatment of malignant neuroblastomas. Therefore, new treatment strategies are urgently needed. We tested the efficacy of combination of SU5416 (SU), an inhibitor of the vascular endothelial growth factor receptor-2 (VEGFR-2), and (-)-epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, for controlling growth of human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells. Combination of 20 μM SU and 50 μM EGCG synergistically inhibited cell survival, suppressed expression of VEGFR-2, inhibited cell migration, caused cell cycle arrest, and induced apoptosis. Combination of SU and EGCG effectively blocked angiogenic and survival pathways and modulated expression of cell cycle regulators. Apoptosis was induced by down regulation of Bcl-2, activation of caspase-3, and cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). Taken together, this combination of drugs can be a promising therapeutic strategy for controlling the growth of human malignant neuroblastoma cells.
摘要
恶性神经母细胞瘤是儿童的实体肿瘤。现有的治疗药物对于恶性神经母细胞瘤的治疗效果并不高。因此，迫切需要新的治疗策略。我们测试了 SU5416（SU）和表没食子儿茶素没食子酸酯（EGCG）联合应用抑制血管内皮生长因子受体-2（VEGFR-2）和绿茶中的多酚化合物，以控制人恶性神经母细胞瘤 SH-SY5Y 和 SK-N-BE2 细胞生长的疗效。20μM SU 和 50μM EGCG 的联合使用协同抑制细胞存活，抑制 VEGFR-2 的表达，抑制细胞迁移，引起细胞周期停滞，并诱导细胞凋亡。SU 和 EGCG 的联合使用有效地阻断了血管生成和存活途径，并调节了细胞周期调节剂的表达。细胞凋亡是通过下调 Bcl-2、激活 caspase-3 和切割 DNA 修复酶聚（ADP-核糖）聚合酶（PARP）诱导的。总之，这种药物联合应用可能是控制人恶性神经母细胞瘤细胞生长的一种有前途的治疗策略。
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