Apoptosis induced by cisplatin nephrotoxic injury
Apoptosis induced by cisplatin nephrotoxic injury
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DOI：
10.1046/j.1523-1755.1999.00687.x
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发表时间：
1999-10-01
影响因子：
19.6
通讯作者：
Lau, AH
中科院分区：
文献类型：
--
作者：
Lau, AH
顺铂是一种常用于癌症治疗的药物，即使是单次给药也可能导致急性肾衰竭。最近的实验室研究证实顺铂诱导肾细胞凋亡。细胞活力降低以及细胞核碎裂的细胞数量增加与顺铂暴露呈剂量依赖性相关。凝胶电泳显示存在一个特征性的梯状模式，这是由caspase-3活性的增加之前。随着顺铂浓度增加超过50 μ M，caspase-3活性的升高下降，这表明坏死而不是凋亡更可能是继发于较高顺铂浓度的细胞死亡的原因。阐明顺铂肾毒性的分子机制可能会导致一种新的治疗策略的发展，靶向癌细胞死亡，同时最大限度地减少肾损伤。
An agent often used in cancer treatment, cisplatin may cause acute renal failure after even a single dose. Recent laboratory studies confirmed the induction of renal cell apoptosis by cisplatin. Reduction in cell viability as well as increase in the number of cells with fragmented nuclei correlated with cisplatin exposure in a dose-dependent manner. Gel electrophoresis revealed the presence of a characteristic laddering pattern which was preceded by an increase in caspase-3 activity. As the cisplatin concentration increased beyond 50 mu M, the elevation of caspase-3 activity declined, which suggests that necrosis, instead of apoptosis, is more likely to be responsible for cell death secondary to higher cisplatin concentrations. Elucidation of the molecular mechanisms of cisplatin nephrotoxicity may lead to the development of a novel therapeutic strategy that targets cancer cell death while simultaneously minimizing renal injury.