High LET radiation enhances nocodazole Induced cell death in HeLa cells through mitotic catastrophe and apoptosis.
High LET radiation enhances nocodazole Induced cell death in HeLa cells through mitotic catastrophe and apoptosis.
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DOI：
10.1269/jrr.10186
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发表时间：
2011-07
影响因子：
2
通讯作者：
Ping Li;Libin Zhou;Z. Dai;Xiaodong Jin;Xinguo Liu;Y. Matsumoto;Y. Furusawa;Qiang Li
中科院分区：
文献类型：
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作者：
Ping Li;Libin Zhou;Z. Dai;Xiaodong Jin;Xinguo Liu;Y. Matsumoto;Y. Furusawa;Qiang Li
为了了解人类肿瘤细胞对诺考达唑和高 LET 辐射联合治疗的反应，本研究对细胞周期的改变、有丝分裂紊乱和细胞死亡进行了研究。将人宫颈癌 HeLa 细胞暴露于诺考达唑 18 小时，然后立即进行高 LET 铁离子照射，并显示出一系列导致 DNA 损伤、有丝分裂畸变、间期恢复和内周期以及细胞死亡的事件。无论是否存在辐射，诺考达唑暴露后都观察到有丝分裂停滞超过 10 小时。有丝分裂停滞后有丝分裂滑移的发生仅依赖于药物，并且辐射不会加速有丝分裂滑移。有丝分裂滑移后多倍体细胞的数量增加。联合治疗后，细胞中未观察到可检测到的 G(2) 或 G(1) 停滞，并且细胞重新进入细胞周期，但仍带有未修复的细胞损伤。这种过早进入导致多极有丝分裂纺锤体的增加和中心体的扩增，从而导致染色体材料滞后、胞质分裂和多倍化的失败。这些有丝分裂紊乱及其结果证实了联合治疗后 TUNEL 方法显示的有丝分裂灾难和延迟凋亡特征的发生率。这些结果表明，在诺考达唑中加入高 LET 铁离子照射会增强 HeLa 细胞的有丝分裂灾难并延迟细胞凋亡。这些可能是肿瘤细胞响应抗有丝分裂药物联合高 LET 辐射治疗的重要细胞死亡机制。
To understand how human tumor cells respond to the combined treatment with nocodazole and high LET radiation, alterations in cell cycle, mitotic disturbances and cell death were investigated in the present study. Human cervix carcinoma HeLa cells were exposed to nocodazole for 18 h immediately followed by high LET iron ion irradiation and displayed a sequence of events leading to DNA damages, mitotic aberrations, interphase restitution and endocycle as well as cell death. A prolonged mitotic arrest more than 10 h was observed following nocodazole exposure, no matter the irradiation was present or not. The occurrence of mitotic slippage following the mitotic arrest was only drug-dependent and the irradiation did not accelerate it. The amount of polyploidy cells was increased following mitotic slippage. No detectable G(2) or G(1) arrest was observed in cells upon the combined treatment and the cells reentered the cell cycle still harboring unrepaired cellular damages. This premature entry caused an increase of multipolar mitotic spindles and amplification of centrosomes, which gave rise to lagging chromosomal material, failure of cytokinesis and polyploidization. These mitotic disturbances and their outcomes confirmed the incidence of mitotic catastrophe and delayed apoptotic features displayed by TUNEL method after the combined treatment. These results suggest that the addition of high-LET iron ion irradiation to nocodazole enhanced mitotic catastrophe and delayed apoptosis in HeLa cells. These might be important cell death mechanisms involved in tumor cells in response to the treatment of antimitotic drug combined with high LET radiation.