Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement
| Autor: | Cheng Jen Chuong, Digant P. Davé, Loan Bui, Alissa Hendricks, Robert Bachoo, Young Tae Kim, Jamie Wright |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Proto-Oncogene Proteins B-raf Pathology medicine.medical_specialty Paclitaxel Cell Survival Brain tumor Drug resistance Biology Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Neuroblastoma medicine Tumor Cells Cultured PTEN Animals Humans Multidisciplinary Wild type PTEN Phosphohydrolase medicine.disease Antineoplastic Agents Phytogenic 030104 developmental biology chemistry Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis Astrocytes biology.protein Cancer research |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep26134 |
| Popis: | Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII) and genetically modified mouse astrocytes (wild type, p53−/−, p53−/− PTEN−/−, p53−/− Braf and p53−/− PTEN−/− Braf). We found that loss of PTEN combined with Braf activation resulted in higher viability in narrow microchannels. In addition, Braf conferred increased resistance to the microtubule-stabilizing drug Taxol in narrow confinement. Similarly, survival of D54-EGFRvIII cells was unaffected following treatment with Taxol, whereas the viability of D54 cells was reduced by 75% under these conditions. Taken together, our data suggests key targets for anticancer drugs based on cellular genotypes and their specific survival phenotypes during confined migration. |
| Databáze: | OpenAIRE |
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