Real-time monitoring of cisplatin-induced cell death.
Real-time monitoring of cisplatin-induced cell death.
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DOI：
10.1371/journal.pone.0019714
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wölfl S
中科院分区：
文献类型：
--
作者：
Alborzinia H;Can S;Holenya P;Scholl C;Lederer E;Kitanovic I;Wölfl S
自从40多年前发现顺铂并在20世纪70年代将其引入临床以来，大量的研究已经进入阐明顺铂对肿瘤细胞的作用机制。通过新型细胞生物传感器芯片系统，可以连续监测呼吸、糖酵解和阻抗，我们实时跟踪了不同癌细胞系的顺铂治疗。我们的测量揭示了在所有顺铂处理的细胞系中对呼吸的第一影响，随后在HT-29、HCT-116、HepG 2和MCF-7细胞中通过干扰糖酵解而显着延迟，但在顺铂耐药细胞系MDA-MB-231中没有。最引人注目的是，所有顺铂敏感细胞系在治疗后8至11小时内开始细胞死亡，这表明从暴露、对顺铂损伤的首次反应到细胞命运决定有一个明确的时间框架。选择最显著变化的时间点，以更详细地分析乳腺癌细胞系MCF-7中的顺铂反应。在糖酵解和阻抗发生变化的时间点直接从传感器芯片获得的样品中分析了与细胞增殖相关的选定信号转导介质的磷酸化以及基因表达的变化。我们的在线细胞生物传感器测量首次揭示了顺铂治疗下细胞死亡发生之前的代谢反应的时间尺度，这与p53介导的细胞命运决定模型非常一致。
Since the discovery of cisplatin more than 40 years ago and its clinical introduction in the 1970s an enormous amount of research has gone into elucidating the mechanism of action of cisplatin on tumor cells. With a novel cell biosensor chip system allowing continuous monitoring of respiration, glycolysis, and impedance we followed cisplatin treatment of different cancer cell lines in real-time. Our measurements reveal a first effect on respiration, in all cisplatin treated cell lines, followed with a significant delay by interference with glycolysis in HT-29, HCT-116, HepG2, and MCF-7 cells but not in the cisplatin-resistant cell line MDA-MB-231. Most strikingly, cell death started in all cisplatin-sensitive cell lines within 8 to 11 h of treatment, indicating a clear time frame from exposure, first response to cisplatin lesions, to cell fate decision. The time points of most significant changes were selected for more detailed analysis of cisplatin response in the breast cancer cell line MCF-7. Phosphorylation of selected signal transduction mediators connected with cellular proliferation, as well as changes in gene expression, were analyzed in samples obtained directly from sensor chips at the time points when changes in glycolysis and impedance occurred. Our online cell biosensor measurements reveal for the first time the time scale of metabolic response until onset of cell death under cisplatin treatment, which is in good agreement with models of p53-mediated cell fate decision.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
3.3
作者：
Kim, YK;Kim, HJ;Kim, JM
通讯作者：
Kim, JM
影响因子：
3.7
作者：
Wegener, J;Keese, CR;Giaever, I
通讯作者：
Giaever, I
影响因子：
4.8
作者：
Wang, XT;Martindale, JL;Holbrook, NJ
通讯作者：
Holbrook, NJ
影响因子：
4.8
作者：
Kim, Hak-Su;Hwang, Jin-Taek;Ha, Joohun
通讯作者：
Ha, Joohun