Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells.

摘要: Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multimodal treatment with surgery and chemo/radiotherapies. GBM-initiating cells (GICs) are likely cell-of-origin in recurrences, as they proliferate indefinitely, form tumors vivo, resistant to It is therefore crucial find chemicals that specifically kill GICs. We established temozolomide (the standard medicine for GBM)-resistant GICs (GICRs) used chemical screening. Here, we identified 1-(3-C-ethynyl-β-d-ribopentofuranosyl) uracil (EUrd) a selective drug targeting GICRs. EUrd induced death GICRs more effectively than their parental GICs, while it was less toxic normal neural stem cells. demonstrate cytotoxic effect on partly depended increased expression uridine-cytidine kinase-like 1 (UCKL1) decreased 5'-nucleotidase cytosolic III (NT5C3), which regulate uridine-monophosphate synthesis positively negatively respectively. Together, these findings suggest can be new therapeutic GBM surrogate markers UCKL1 NT5C3. Stem Cells 2016;34:2016-2025.