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

Lijuan Ding, Changji Yuan, Feng Wei, Guangyi Wang, Jing Zhang, Anita C. Bellail, Zhaobin Zhang, Jeffrey J. Olson, Chunhai Hao

Research output: Contribution to journalArticle

45 Scopus citations

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-1β-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.

Original languageEnglish (US)
Pages (from-to)511-520
Number of pages10
JournalCancer Investigation
Volume29
Issue number8
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

Keywords

  • Apoptosis
  • Cancer stem cell
  • Cisplatin
  • Glioblastoma
  • TRAIL

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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