Cytotoxic effects of 125I-labeled PBZr ligand PK 11195 in prostatic tumor cells:: therapeutic implications
Cytotoxic effects of 125I-labeled PBZr ligand PK 11195 in prostatic tumor cells:: therapeutic implications
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DOI：
10.1016/s0304-3835(98)00258-4
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发表时间：
1998-12-25
期刊：
影响因子：
9.7
通讯作者：
Batra, S
中科院分区：
文献类型：
--
作者：
Alenfall, J;Kant, R;Batra, S
在培养的人前列腺肿瘤细胞（DU 145）中检查了[I-125]PK 11195的作用，并与Na[I-125]和非放射性PK 11195进行了比较，[I-125]PK 11195具有明显的杀细胞作用。剂量相关细胞存活率与[I-125]PK 11195的数据显示线性关系。相似浓度的Na[I-125]或非标记PK 11195未导致任何细胞杀伤。[I-125]PK 11195和[H-3]PK 11195在细胞中的摄取非常相似。琼脂糖凝胶电泳测定的DNA片段显示DU 145细胞暴露于[I-125]PK 11195 1、4或24 h均未引起DNA片段化。这些结果表明，核DNA不是[I-125]PK 11195的主要结合位点，这与线粒体中存在特异性外周苯二氮卓类受体（PBZr）一致。[I-125]PK 11195的细胞杀伤作用提示PBZr配体可用于放射治疗。(C)1998爱思唯尔科学爱尔兰有限公司保留所有权利。
The effect of [I-125]PK 11195 was examined in human prostatic tumor cells (DU 145) in culture and compared with Na[I-125] and non-radioactive PK 11195, [I-125]PK 11195 was clearly cytocidal. The data for dose-related cell survival with [I-125]PK 11195 showed a linear relationship. Na[I-125] or non-labeled PK 11195 at similar concentrations did not lead to any cell killing. The uptake of [I-125]PK 11195 and [H-3]PK 11195 in cells was very similar. Fragmentation of DNA measured by agarose gel electrophoresis showed that exposure of DU 145 cells to [I-125]PK 11195 for 1, 4 or 24 h caused no fragmentation. These results indicate that nuclear DNA is not the prime binding site for [I-125]PK 11195, which is consistent with the presence of specific peripheral benzodiazepine receptors (PBZr) in the mitochondria. The cell killing effect of [I-125]PK 11195 suggests the use of PBZr ligand for radiotherapy. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.