期刊
CANCER LETTERS
卷 324, 期 2, 页码 171-178出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.05.009
关键词
Cisplatin resistance; Germ cell tumours (GCTs); DNA platination; gamma H2AX; DNA damage response; Cell cycle response
类别
资金
- Ernst und Elfriede Griebel's Foerderungs- und Unterstuetzungsstiftung, Hamburg
- Werner Otto Stiftung, Hamburg
To identify factors involved in cisplatin (CDDP) resistance of germ cell tumours (GCTs), we exposed NTERA-2 cells, and the platinum-adapted subline NTERA-2R to CDDP and compared their response. While both cell lines showed comparable proliferation, NTERA-2R cells were clearly more resistant to the drug than the parental NTERA-2 cell line. Interestingly, the two lines showed identical extent of DNA adduct formation and elimination, indicating that neither changes in CDDP uptake, nor altered drug efflux, DNA binding, or repair caused the difference in resistance. Similarly, no difference occurred in the time-course of gamma H2AX formation, which was not linked to 53BP1 accumulation. In contrast, NTERA-2R cells showed a more pronounced dose-dependent S phase delay, a transient G(2)/M-block, and subsequent release into immediate cell death. We thus conclude that the enhanced resistance against CDDP is linked to reduced susceptibility to cell death rather than to an altered DNA adduct formation or adduct removal. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据