Cabazitaxel overcomes cisplatin resistance in germ cell tumour cells
| Autor: | Jessica Hauschild, Karin Oechsle, Gunhild von Amsberg, Mirjam Gerwing, Carsten Bokemeyer, Jan Oldenburg, Tina Rohlfing, Friedemann Honecker, Christoph Oing, Simone Venz, Christine Jacobsen, Sergey A. Dyshlovoy |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty Paclitaxel medicine.medical_treatment Salvage therapy Antineoplastic Agents Apoptosis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Testicular Neoplasms Internal medicine Cell Line Tumor Medicine Humans Cisplatin Chemotherapy Taxane business.industry Cell Cycle General Medicine Cell cycle Neoplasms Germ Cell and Embryonal 030104 developmental biology medicine.anatomical_structure chemistry Cabazitaxel Drug Resistance Neoplasm 030220 oncology & carcinogenesis Taxoids business Germ cell medicine.drug |
| Zdroj: | Journal of cancer research and clinical oncology. 142(9) |
| ISSN: | 1432-1335 |
| Popis: | Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines.In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array.Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT.Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance. |
| Databáze: | OpenAIRE |
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