Proapoptotic effects of NF-κB on cisplatin-induced cell death in auditory cell line
Proapoptotic effects of NF-κB on cisplatin-induced cell death in auditory cell line
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DOI：
10.1080/00016480701881811
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发表时间：
2008-01-01
影响因子：
1.4
通讯作者：
Hong, Sung Hwa
中科院分区：
文献类型：
--
作者：
Chung, Won-Ho;Boo, Sung Hyun;Hong, Sung Hwa
结论。研究结果表明，核因子 (NF)-kappa B 被顺铂激活，并在听觉细胞系 HEI-OC1 的细胞死亡过程中发挥促凋亡作用。目标。顺铂是一种非常有效的抗肿瘤药物，但在高剂量时，它会通过诱导耳蜗毛细胞凋亡而表现出耳毒性。 NF-kappa B 是调节许多器官和组织细胞凋亡的转录因子。本研究探讨了 NF-kappa B 在顺铂诱导的听觉细胞系 HEI-OC1 细胞凋亡途径中的作用。材料和方法。顺铂处理 (50 M) 24 小时后，通过测量 caspase 3 活性和抗 caspase 3 抗体免疫染色来鉴定细胞凋亡。为了研究 NF-κ B 在细胞凋亡中的作用，用 50 M 顺铂处理的 HEI-OC1 细胞用抗 NF-κ B (p65) 抗体进行免疫染色。将两种不同的 NF-κ B 抑制剂 Bay 11-7085 和 SN-50 与顺铂 (50 M) 共孵育 24 小时，并测定 caspase 3 活性。结果。抗Caspase 3抗体免疫染色和Caspase 3测定表明顺铂诱导HEI-OC1细胞凋亡。顺铂处理后，NF-kappa B (p65) 被激活，从细胞质易位至细胞核。与 NF-κ B 抑制剂共同治疗可减少顺铂诱导的 HEI-OC1 细胞凋亡。
Conclusions. The findings suggest that nuclear factor (NF)-kappa B is activated by cisplatin and plays a proapoptotic role during cell death in the auditory cell line HEI-OC1. Objectives. Cisplatin is a very effective antineoplastic drug but in high doses it shows ototoxicity by inducing apoptosis of hair cells in the cochlea. NF-kappa B is a transcription factor regulating apoptosis in many organs and tissues. This study examined the role of NF-kappa B in the apoptotic pathway induced by cisplatin in the auditory cell line, HEI-OC1. Materials and methods. Apoptotic cell death was identified by measuring caspase 3 activity and immunostaining with anti-caspase 3 antibody after cisplatin treatment (50 M) for 24 h. To investigate the role of NF-kappa B in apoptotic cell death, HEI-OC1 cells treated with 50 M of cisplatin were immunostained with anti-NF-kappa B (p65) antibody. Two different NF-kappa B inhibitors, Bay 11-7085 and SN-50, were co-incubated with cisplatin (50 M) for 24 h and caspase 3 activity was assayed. Results. Immunostaining with anti-caspase 3 antibody and caspase 3 assay showed that cisplatin induced apoptosis in HEI-OC1 cells. After cisplatin treatment, NF-kappa B (p65) was activated to translocate from the cytoplasm into the nucleus. Co-treatment with NF-kappa B inhibitors reduced the cisplatin-induced apoptosis of HEI-OC1 cells.