Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement

Loan Bui, Alissa Hendricks, Jamie Wright, Cheng Jen Chuong, Digant Davé, Robert Bachoo, Young Tae Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Article number26134
JournalScientific Reports
Volume6
DOIs
StatePublished - May 17 2016

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Paclitaxel
Brain Neoplasms
Cell Line
Survival
Glioblastoma
Neuroblastoma
Drug Resistance
Microtubules
Astrocytes
Pharmaceutical Preparations
Neoplasms
Cell Survival
Genotype
Radiation
Phenotype
Drug Therapy
Equipment and Supplies
epidermal growth factor receptor VIII
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement. / Bui, Loan; Hendricks, Alissa; Wright, Jamie; Chuong, Cheng Jen; Davé, Digant; Bachoo, Robert; Kim, Young Tae.

In: Scientific Reports, Vol. 6, 26134, 17.05.2016.

Research output: Contribution to journalArticle

Bui, Loan ; Hendricks, Alissa ; Wright, Jamie ; Chuong, Cheng Jen ; Davé, Digant ; Bachoo, Robert ; Kim, Young Tae. / Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement. In: Scientific Reports. 2016 ; Vol. 6.
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AU - Kim, Young Tae

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