Cisplatin resistance induced in germ cell tumour cells is due to reduced susceptibility towards cell death but not to altered DNA damage induction or repair

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• 作者：Annabelle E. Fenske ; Stephanie Glaesener ; Carsten Bokemeyer ; Juergen Thomale ; Jochen Dahm-Daphi ; Friedemann Honecker ; Dorothee C. Dartsch
• 关键词：CDDP ; cisplatin ; DSB ; double strand break ; GCT ; germ cell tumour
• 刊名：Cancer Letters
• 出版年：2012
• 出版时间：28 November, 2012
• 年：2012
• 卷：324
• 期：2
• 页码：171-178
• 全文大小：666 K

文摘

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 ¦ÃH2AX formation, which was not linked to 53BP1 accumulation. In contrast, NTERA-2R cells showed a more pronounced dose-dependent S phase delay, a transient Gub>2ub>/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.