Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement.
Sci Rep
; 6: 26134, 2016 05 17.
Article
em En
| MEDLINE
| ID: mdl-27184621
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Astrócitos
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Paclitaxel
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Resistencia a Medicamentos Antineoplásicos
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Antineoplásicos Fitogênicos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article