Santamaria Hospital, 13-15 Shinjo-cho, Ibaraki, Osaka 567-0884, Japan.
Oncol Rep. 2012 Jul;28(1):330-6. doi: 10.3892/or.2012.1774. Epub 2012 Apr 23.
A recent study showed that both 5-fluorouracil (5FU)-stimulated apoptosis and Fas-mediated apoptosis in human endometrial adenocarcinoma cells are enhanced by targeted knockdown of endogenous death-associated protein kinase (DAPK) with DAPK small-interfering RNAs. Therefore, we investigated the DAPK survival signals in three 5FU-resistant subclones. DAPK knockdown did not enhance 5FU-stimulated or Fas-mediated apoptosis in any of the three 5FU-resistant subclones, but the subclones acquired resistance to VP16-stimulated cell death that was DAPK-independent. Semi-quantitative flow cytometric analyses showed that there was no differential expression in nine cell surface antigens, including Fas, and six intracellular molecules, including DAPK, that may regulate cell death or survival between the parent cells and 5FU-resistant cells. DAPK mRNA and protein were expressed in the 5FU-resistant subclones at similar levels to the parent cells. These results indicate that acquisition of 5FU-resistance may be accompanied by impairment of common apoptotic signals regulating both DAPK-dependent and DAPK-independent pathways.
最近的一项研究表明，通过 DAPK 小干扰 RNA 靶向敲低内源性凋亡相关蛋白激酶（DAPK），可增强人子宫内膜腺癌细胞中 5-氟尿嘧啶（5FU）刺激的凋亡和 Fas 介导的凋亡。因此，我们在三个 5FU 耐药亚克隆中研究了 DAPK 的生存信号。DAPK 敲低并未增强三种 5FU 耐药亚克隆中的 5FU 刺激或 Fas 介导的凋亡，但亚克隆获得了对 VP16 刺激细胞死亡的耐药性，这种耐药性与 DAPK 无关。半定量流式细胞术分析显示，在亲本细胞和 5FU 耐药细胞之间，可能调节细胞死亡或存活的九个细胞表面抗原（包括 Fas）和六个细胞内分子（包括 DAPK）中没有差异表达。DAPK mRNA 和蛋白在 5FU 耐药亚克隆中的表达水平与亲本细胞相似。这些结果表明，获得 5FU 耐药性可能伴随着调节 DAPK 依赖性和 DAPK 非依赖性途径的共同凋亡信号的损害。
