Efficacy of targeted drugs in germ cell cancer cell lines with differential cisplatin sensitivity

• Published in: PloS one 2017-06, Vol.12 (6), p.e0178930-e0178930
• Main Authors: Schaffrath, Judith, Schmoll, Hans-Joachim, Voigt, Wieland, Müller, Lutz P, Müller-Tidow, Carsten, Mueller, Thomas
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Biology and Life Sciences; Biotechnology; Cancer; Cancer therapies; Care and treatment; Cell cycle; Cell growth; Cell Line, Tumor; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Cisplatin - therapeutic use; Complications and side effects; Cytotoxicity; Development and progression; Dosage and administration; Dose-Response Relationship, Drug; Drugs; Epidermal growth factor; Epidermal growth factor receptors; ErbB-2 protein; Everolimus - pharmacology; Everolimus - therapeutic use; Ewings sarcoma; Genetic aspects; Germinoma; Growth inhibition; Hematology; Humans; In vitro methods and tests; Inhibitors; Inhibitory Concentration 50; Insulin; Insulin-like growth factors; Internal medicine; Kinases; Medical prognosis; Medicine; Medicine and Health Sciences; Men; Monoclonal antibodies; Multiple myeloma; Mutation; Neoplasms, Germ Cell and Embryonal - drug therapy; Neoplasms, Germ Cell and Embryonal - pathology; Oncology; Patients; Phosphorylation; Phosphorylation - drug effects; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Purines - pharmacology; Purines - therapeutic use; Receptors; Response rates; Testicular Neoplasms - drug therapy; Testicular Neoplasms - pathology; TOR protein; Toxicity; Tumor cell lines; Tumors; Vascular endothelial growth factor; Vascular endothelial growth factor receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0178930

The in vitro activity of kinase inhibitors targeting mTOR (RAD001), EGFR, HER2/neu, VEGFR (AEE788) and IGF-1R (AEW541) alone or in combination with cisplatin was tested in the cisplatin sensitive TGCT cell lines H12.1 and GCT72 as well as in the resistant cell lines H12.1RA, H12.1D, 1411HP and 1777NRpmet using the sulforhodamin-B-(SRB)-cytotoxicity-assay. To evaluate the activity of the kinase inhibitors, western blot analysis of the targeted receptors and their phosphorylated state was performed before and after exposure to each substance. The different kinase inhibitors demonstrated significant cell growth inhibition in both cisplatin sensitive and resistant cell lines. The examined cell lines showed different protein expression levels of the targeted receptors. However there was no correlation between the targeted receptor expression and phosphorylation level and the antiproliferative effect of the respective agent. Furthermore, the combination of cisplatin and the kinase inhibitors exerted both additive and antagonistic effects in the studied cell lines. Our data suggest potential activity of the investigated kinase inhibitors in both cisplatin sensitive and resistant TGCT cell lines as a single agent. However, when combined with cisplatin they did not demonstrate any promising ability to overcome cisplatin resistance in TGCTs.