Eugenia Yazlovitskaya
Faculty Member
Last active: 11/16/2017

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.

Cui W, Yazlovitskaya EM, Mayo MS, Pelling JC, Persons DL
Mol Carcinog. 2000 29 (4): 219-28

PMID: 11170260

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 all 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.

MeSH Terms (17)

Antineoplastic Agents Cell Survival Cisplatin Dose-Response Relationship, Drug Drug Resistance, Neoplasm Enzyme Activation Enzyme Inhibitors Female Flavonoids Humans JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Ovarian Neoplasms Time Factors Tumor Cells, Cultured

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