Glioblastoma-derived cells in vitro unveil the spectrum of drug resistance capability – comparative study of tumour chemosensitivity in different culture systems
| Autor: | Wielisław Papierz, Magdalena Zakrzewska, Monika Witusik-Perkowska, Beata Sikorska, Dariusz J. Jaskólski, Pawel P. Liberski, Janusz Szemraj |
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| Rok vydání: | 2017 |
| Předmět: |
cancer stem cells
0301 basic medicine cancer drug resistance Cell Apoptosis Drug resistance Pharmacology Biochemistry Culture Media Serum-Free 0302 clinical medicine Tumor Cells Cultured Research Articles Brain Neoplasms Cell Cycle Cell cycle Dacarbazine medicine.anatomical_structure 030220 oncology & carcinogenesis epithelial-to-mesenchymal transition Research Article autophagy Programmed cell death Epithelial-Mesenchymal Transition Cell Survival Primary Cell Culture Biophysics Antineoplastic Agents Biology Statistics Nonparametric 03 medical and health sciences Cancer stem cell Temozolomide medicine Humans Neoplasm Invasiveness Molecular Biology cell culture Gene Expression Profiling glioblastoma Cell Biology Gene expression profiling Tamoxifen 030104 developmental biology Drug Resistance Neoplasm Cell culture Cancer cell Cancer research |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 0144-8463 |
| DOI: | 10.1042/bsr20170058 |
| Popis: | Resistance to cancer drugs is a complex phenomenon which could be influenced by in vitro conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three in vitro models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture. The experimental models were evaluated according to ‘stemness state‘ and epithelial-to-mesenchymal transition (EMT) status, invasion capability and their expression pattern of genes related to the phenomenon of tumour drug resistance. Additionally, the response to drug treatments of three different culture models was compared with regard to the type of cell death. Multi-gene expression profiling revealed differences between examined culture types with regard to the expression pattern of the selected genes. Functionally, the examined genes were related to drug resistance and metabolism, DNA damage and repair and cell cycle control, and included potential therapeutic targets. Cytotoxicity analyses confirmed that environmental factors can influence not only the molecular background of glioblastoma drug-resistance and efficiency of treatment, but also the mechanisms/pathways of cell death, which was reflected by a distinct intensification of apoptosis and autophagy observed in particular culture models. Our results suggest that parallel exploitation of different in vitro experimental models can be used to reveal the spectrum of cancer cell resistance capability, especially regarding intra-heterogeneous glioblastomas. |
| Databáze: | OpenAIRE |
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