Viability fingerprint of glioblastoma cell lines: roles of mitotic, proliferative, and epigenetic targets
| Autor: | Tõnis Laasfeld, Darja Lavogina, M. Vardja, Helen Lust, Jana Jaal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell biology
DNA damage DNA repair Science Cell Biology DNA methyltransferase Article Epigenesis Genetic Aurora kinase Lomustine Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Temozolomide Humans Epigenetics Cancer Multidisciplinary Brain Neoplasms Cell Cycle Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Cancer research Azacitidine Medicine Glioblastoma medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Despite the use of multimodal treatment combinations, the prognosis of glioblastoma (GB) is still poor. To prevent rapid tumor recurrence, targeted strategies for the treatment of GB are widely sought. Here, we compared the efficacy of focused modulation of a set of signaling pathways in two GB cell lines, U-251 MG and T98-G, using a panel of thirteen compounds targeting cell cycle progression, proliferation, epigenetic modifications, and DNA repair mechanism. In parallel, we tested combinations of these compounds with temozolomide and lomustine, the standard chemotherapy agents used in GB treatment. Two major trends were found: within individual compounds, the lowest IC50 values were exhibited by the Aurora kinase inhibitors, whereas in the case of mixtures, the addition of DNA methyltransferase 1 inhibitor azacytidine to lomustine proved the most beneficial. The efficacy of cell cycle-targeting compounds was further augmented by combination with radiation therapy using two different treatment regimes. The potency of azacytidine and lomustine mixtures was validated using a unique assay pipeline that utilizes automated imaging and machine learning-based data analysis algorithm for assessment of cell number and DNA damage extent. Based on our results, the combination of azacytidine and lomustine should be tested in GB clinical trials. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink