Abstract | BACKGROUND: MATERIALS AND METHODS: For this exploratory study, we screened MPM cell lines (NCI-H2452, NCI-H2052, and MSTO-211H) differing in response to cisplatin and benign control fibroblasts (MRC-5) for overall phosphorylation patterns as well as kinase activity with respect to cellular response to cisplatin-based therapeutics. We analysed the cell lines for cellular kinases in a high-throughput manner using the highly innovative technique PamGene. Cell state analysis including apoptosis, necrosis, and cell viability was performed by using enzyme activity and fluorescent-based assays. RESULTS:
Cisplatin alters cellular phosphorylation patterns affecting cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis. In cisplatin-responsive cell lines, phosphorylation of AKT1 and GSK3B was decreased but could not be influenced in cisplatin-resistant NCI-H2452 cells. Cisplatin-responsive cell lines showed increased phosphorylation levels of JNK1/2/3 but decreased phosphorylation in cisplatin-resistant NCI-H2452 cells. CONCLUSION:
Kinase phosphorylation and activity might play a crucial role in cellular response to cytostatic agents. Cisplatin influences phosphorylation patterns with distinct features in cisplatin-resistant cells. These alterations exert a significant impact on cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis of the respective tumor cells. Based on our results, the induction of p38 or JNK1/3, or inhibition of AKT1 by, for example, BIA-6, might offer a positive synergistic effect by induction of an apoptotic response to cisplatin-based treatment, thus potentially enhancing the clinical outcome of MPM patients.
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Authors | Sabrina Borchert, Pia-Maria Suckrau, Michael Wessolly, Elena Mairinger, Balazs Hegedus, Thomas Hager, Thomas Herold, Wildfried E E Eberhardt, Jeremias Wohlschlaeger, Clemens Aigner, Agnes Bankfalvi, Kurt Werner Schmid, Robert F H Walter, Fabian D Mairinger |
Journal | Journal of oncology
(J Oncol)
Vol. 2019
Pg. 2902985
( 2019)
ISSN: 1687-8450 [Print] Egypt |
PMID | 31929796
(Publication Type: Journal Article)
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Copyright | Copyright © 2019 Sabrina Borchert et al. |