Effect Of Interferon-Alpha/Beta On Temozolomide Activity Against Mgmt-Positive Glioma Stem-Like Cells In Vitro And In Vivo.

JOURNAL OF CLINICAL ONCOLOGY(2012)

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Abstract
e12503 Background: O6-methylguanine DNA methyltranferase (MGMT) is one of the main mechanisms of chemoresistance for alkylating agents in malignant gliomas. Recent studies have showed that glioma stem-like cells (GSCs) could be the main reason for tumor recurrence and chemoresistance. In this study, we aimed to explore the effects of interferon-α/β against MGMT-positive glioma stem-like cells, and to investigate whether interferon-α/β can enhance the efficiency of temozolomide (TMZ) and the possible mechanism Methods: The growth inhibition effect of TMZ, with interferon-α or interferon-β, against the MGMT-positive GSCs from human glioma cell lines U251 and SKMG-4 (U251G and SKMG-4G) was evaluated by using Cell Counting Kit-8 (CCK-8) assay in vitro, and in xenograft models. MGMT and NF-κB expression in the tumor samples were determined by RT-PCR and Western blot analysis. Results: Our results revealed that the anti-tumor activity of TMZ was significantly enhanced by combined using interferon-α/β in vitro. ...
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