Cisplatin-induced response of c-jun N-terminal kinase 1 and extracellular signal-regulated protein kinases 1 and 2 in a series of cisplatin-resistant ovarian carcinoma cell lines
Cisplatin-induced response of c-jun N-terminal kinase 1 and extracellular signal-regulated protein kinases 1 and 2 in a series of cisplatin-resistant ovarian carcinoma cell lines
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DOI：
10.1002/1098-2744(200012)29:4
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发表时间：
2000-12-01
影响因子：
4.6
通讯作者：
Persons, DL
中科院分区：
文献类型：
--
作者：
Cui, W;Yazlovitskaya, EM;Persons, DL
细胞对顺铂的反应涉及多种信号转导途径的激活，包括丝裂原活化蛋白（MAP）激酶途径。在这项研究中，我们比较了顺铂诱导的两种MAP激酶，c-jun n-末端激酶1 （JNK1）和细胞外信号调节蛋白激酶1和2 （ERK1/2）在顺铂敏感的卵巢癌细胞系A2780及其衍生的顺铂耐药细胞系CP70和C200中的活化。JNK1和ERK1/2的剂量依赖性和时间依赖性激活发生在顺铂治疗的三种细胞系中。诱导JNK1和ERK1/2的最大激活需要更高浓度的顺铂，这与顺铂耐药水平的增加有关。此外，使用MAP/ERK激酶1合成抑制剂PD98059抑制顺铂诱导的ERK活化，导致三种细胞系对顺铂的敏感性增强。这些结果表明，顺铂诱导的ERK1/2活性不是CP70和C200细胞获得性顺铂耐药的原因，而是在顺铂敏感和顺铂耐药细胞系中提供一般的细胞保护作用。综上所述，顺铂诱导的JNK1和ERK1/2激活在顺铂敏感性不同的细胞系中表现出不同的模式，抑制顺铂诱导的ERK1/2激活可增强顺铂敏感和顺铂耐药细胞系对顺铂的敏感性。(C) 2000 Wiley-Liss, Inc。
The cellular response to cisplatin involves activation of multiple signal transduction pathways, including the mitogen-activated protein (MAP) kinase pathways. In this study, we compared the cisplatin-induced activation of two MAP kinases, c-jun N-terminal kinase 1 (JNK1) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), in the cisplatin-sensitive ovarian carcinoma cell line A2780 and its derivative cisplatin-resistant cell lines CP70 and C200. Dose-dependent and time-dependent activation of JNK1 and ERK1/2 occurred in each of the three cell lines in response to cisplatin treatment. The requirement of higher concentrations of cisplatin for induction of maximum activation of JNK1 and ERK1/2 was correlated with increased levels of cisplatin resistance. In addition, inhibition of cisplatin-induced ERK activation, using the MAP/ERK kinase 1 synthetic inhibitor PD98059, resulted in enhanced sensitivity to cisplatin in ail three cell lines. These results suggest that cisplatin-induced ERK1/2 activity is not responsible for the acquired cisplatin resistance in CP70 and C200 cells but rather provides a general cytoprotective effect in both cisplatin-sensitive and cisplatin-resistant cell lines. In conclusion, different patterns of cisplatin-induced JNK1 and ERK1/2 activation are observed in cell lines with different levels of cisplatin sensitivity, and inhibition of cisplatin-induced ERK1/2 activation enhances sensitivity to cisplatin in both cisplatin-sensitive and cisplatin-resistant cell lines. (C) 2000 Wiley-Liss, Inc.