PRIMA-1 synergizes with adriamycin to induce cell death in non-small cell lung cancer cells
PRIMA-1 synergizes with adriamycin to induce cell death in non-small cell lung cancer cells
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DOI：
10.1002/jcb.21794
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发表时间：
2008-08-15
影响因子：
4
通讯作者：
Menichini, P.
中科院分区：
文献类型：
--
作者：
Magrini, R.;Russo, D.;Menichini, P.
p53依赖性细胞凋亡对于癌症治疗的功效是重要的，并且携带突变型p53的肿瘤通常对化疗具有抗性。非小细胞肺癌（NSCLC）细胞在用许多细胞毒性药物治疗后通常表现出对凋亡的抗性。新分子PRIMA-1似乎通过恢复突变的p53的转录活性来杀死人类肿瘤细胞。我们研究了三种携带不同p53蛋白的NSCLC细胞系对该药物的凋亡诱导：A549（p53 wt），LX 1（p53 R273 H）和SKMes 1（p53 R280 K）。单独的PRIMA-1不触发细胞凋亡，但显著降低细胞活力。然而，PRIMA-1与阿霉素联合使用时，加强了阿霉素诱导的A549和LX 1细胞凋亡。有趣的是，即使在SKMes 1细胞中，联合处理也引发了强烈的PARP切割，而没有DNA片段化。我们的数据表明，在非小细胞肺癌细胞中，PRIMA-1可能通过凋亡以外的途径诱导细胞死亡，但可能与阿霉素协同作用，引发凋亡反应。
p53-dependent apoptosis is important for the efficacy of cancer treatment, and tumors carrying mutant p53 are often resistant to chemotherapy. Non-small cell lung cancer (NSCLC) cells generally exhibit resistance to apoptosis following treatment with many cytotoxic drugs. The new molecule PRIMA-1 appears to kill human tumor cells by restoring the transcriptional activity to mutated p53. We investigated the induction of apoptosis in response to this drug in three NSCLC cell lines carrying different p53 proteins: A549 (p53wt), LX1 (p53R273H), and SKMes1 (p53R280K). PRIMA-1 alone did not trigger apoptosis but significantly reduced cell viability. However, in combination with adriamycin, PRIMA-1 strengthen the adriamycin-induced apoptosis in A549 and LX1. Interestingly, even in SKMes1 cells, the combined treatment triggered a strong PARP cleavage without DNA fragmentation. Our data suggest that in NSCLC cells, PRIMA-1 may induce cell death through pathways other than apoptosis but may synergize with adriamycin to trigger an apoptotic response.