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顺铂诱导的HeLa细胞凋亡。RNA和蛋白质合成抑制剂、Ca2+螯合剂及锌的作用

Cisplatin-induced apoptosis of HeLa cells. Effect of RNA and protein synthesis inhibitors, Ca2+ chelators and zinc.

作者信息

Velázquez M, Maldonado V, Melendez-Zajgla J

机构信息

Division de Investigación Básica. Instituto Nacional de Cancerología, México DF, Mexico.

出版信息

J Exp Clin Cancer Res. 1998 Sep;17(3):277-84.

PMID:9894762
Abstract

HeLa cells exposed to cisplatin undergo cell death, presenting morphological and biochemical characteristics typical of apoptosis. In this study we demonstrate that this process is independent of RNA and protein synthesis, since it was not inhibited by actinomycin D or cycloheximide. These substances induced apoptosis by themselves, suggesting an unidentified short-lived inhibitor. The presence of Ca2+ chelators (EDTA and EGTA) did not have effect in this process, excluding the participation of extracellular Ca2+ access. Finally, zinc ions inhibited the low molecular weight DNA degradation and the apoptotic bodies production, but not cell death. These results provide an insight into the mechanism of action of one of the most used antineoplastic drug.

摘要

暴露于顺铂的HeLa细胞会发生细胞死亡,呈现出典型的凋亡形态和生化特征。在本研究中,我们证明这一过程独立于RNA和蛋白质合成,因为它不受放线菌素D或环己酰亚胺的抑制。这些物质自身会诱导凋亡,提示存在一种未明确的短寿命抑制剂。Ca2+螯合剂(EDTA和EGTA)在此过程中无作用,排除了细胞外Ca2+内流的参与。最后,锌离子抑制了低分子量DNA降解和凋亡小体的产生,但不抑制细胞死亡。这些结果为最常用的抗肿瘤药物之一的作用机制提供了深入见解。

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