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Cisplatin restores TRAIL apoptotic pathway in glioblastoma-derived stem cells through up-regulation of DR5 and down-regulation of c-FLIP.


ABSTRACT: Glioblastoma-derived stem cells (GSCs) are responsible for the cancer resistance to therapies. We show here that GSC-enriched neurospheres are resistant to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) due to the insufficient expression of the death receptor DR4 and DR5 and the overexpression of cellular Fas-associated death domain-like interleukin-1?-converting enzyme-inhibitory protein (c-FLIP). However, treatment with cisplatin leads to the upregulation of DR5 and downregulation of c-FLIP and restores TRAIL apoptotic pathway in the neurospheres. This study suggests that the combined treatment of TRAIL and cisplatin can induce apoptosis in GSCs and thus provide an effective treatment of glioblastomas.

SUBMITTER: Ding L 

PROVIDER: S-EPMC3255792 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Cisplatin restores TRAIL apoptotic pathway in glioblastoma-derived stem cells through up-regulation of DR5 and down-regulation of c-FLIP.

Ding Lijuan L   Yuan Changji C   Wei Feng F   Wang Guangyi G   Zhang Jing J   Bellail Anita C AC   Zhang Zhaobin Z   Olson Jeffrey J JJ   Hao Chunhai C  

Cancer investigation 20110830 8


Glioblastoma-derived stem cells (GSCs) are responsible for the cancer resistance to therapies. We show here that GSC-enriched neurospheres are resistant to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) due to the insufficient expression of the death receptor DR4 and DR5 and the overexpression of cellular Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP). However, treatment with cisplatin leads to the upregulation of D  ...[more]

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