Effect of interferon-α/β on temozolomide activity against MGMT-positive glioma stem-like cells in vitro and in vivo.

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. In xenograft models, the tumor growth inhibit rate (IR) of TMZ to SKMG-4G and U251G was 35.2%±2.28% and 16.7%±1.96%, respectively. When TMZ combined with interferon-α or interferon-β, the IR to SKMG-4G was 58.4%±4.34% and 63.4%±1.08%; and to U251G was 41.1%±8.66% and 44.5%±1.90%, respectively(P<0.05). The expression of NF-κB and MGMT in MGMT-positive GSCs decreased significantly in both mRNA and protein levels after using interferon-α/β. Conclusions: Our results indicate that IFN-α/β can enhance the sensitivity of TMZ, possibly through down-regulate NF-κB expression resulting in lower MGMT transcription expression.