紫杉醇诱导人白血病HL-60细胞中依赖半胱天冬酶-3的凋亡。
Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by paclitaxel.
作者信息
Lu Ko-Hsiu, Lue Ko-Huang, Liao Hsien-Hua, Lin Keh-Liang, Chung Jing-Gung
机构信息
Department of Orthopaedic Surgery, Chung Shan Medical University Hospital, 110, Section 1, Chien-Kuo N. Road, Taichung 402, Taiwan, Republic of China.
出版信息
Clin Chim Acta. 2005 Jul 1;357(1):65-73. doi: 10.1016/j.cccn.2005.02.003. Epub 2005 Mar 31.
BACKGROUND
Paclitaxel, an antineoplastic drug, inhibits cell growth and cell cycle progression and induces apoptosis in human leukemia HL-60 cells. Caspase-3 plays a direct role in proteolytic cleavage of cellular proteins responsible for progression to apoptosis.
METHODS
We examined the cell morphology and apoptosis in HL-60 cells after exposure to paclitaxel and measured caspase-3 activities with or without z-VAD-fmk (a broad-spectrum caspase inhibitor) pretreatment by flow cytometric analysis and Western blotting.
RESULTS
Together, our results were (1) paclitaxel mainly induced G2/M cell cycle arrest in HL-60 cells (p<0.001); (2) time (p<0.001)- and dose-dependent (p<0.001) apoptosis of HL-60 cells was induced by paclitaxel; (3) in HL-60 cells, z-VAD-fmk blocked paclitaxel-induced apoptosis (12 h: p<0.001; 24 h: p<0.01; 48 h: p<0.01; 72 h: p<0.001) and caspase-3 activation (12 h: p<0.05; 24 h: p<0.01; 48 h: p<0.01; 72 h: p<0.01).
CONCLUSIONS
These results suggest that paclitaxel can induce G2/M cell cycle transition and apoptosis via caspase-3 activity in HL-60 cells.
背景
紫杉醇是一种抗肿瘤药物，可抑制细胞生长和细胞周期进程，并诱导人白血病HL-60细胞凋亡。半胱天冬酶-3在负责凋亡进程的细胞蛋白的蛋白水解切割中起直接作用。
方法
我们检测了紫杉醇处理后HL-60细胞的细胞形态和凋亡情况，并通过流式细胞术分析和蛋白质印迹法测量了有无z-VAD-fmk（一种广谱半胱天冬酶抑制剂）预处理时的半胱天冬酶-3活性。
结果
总体而言，我们的结果如下：（1）紫杉醇主要诱导HL-60细胞发生G2/M期细胞周期阻滞（p<0.001）；（2）紫杉醇诱导HL-60细胞发生时间依赖性（p<0.001）和剂量依赖性（p<0.001）凋亡；（3）在HL-60细胞中，z-VAD-fmk可阻断紫杉醇诱导的凋亡（12小时：p<0.001；24小时：p<0.01；48小时：p<0.01；72小时：p<0.001）和半胱天冬酶-3激活（12小时：p<0.05；24小时：p<0.01；48小时：p<0.01；72小时：p<0.01）。
结论
这些结果表明，紫杉醇可通过HL-60细胞中的半胱天冬酶-3活性诱导G2/M期细胞周期转变和凋亡。
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