Interferon-α/β enhances temozolomide activity against MGMT-positive glioma stem-like cells

Sep 3, 2015Oncology reports

Interferon alpha/beta may increase temozolomide's effectiveness against resistant glioma stem-like cells

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Treatment with interferon-α/β markedly enhanced the efficacy of temozolomide against MGMT-positive glioma stem-like cells.

Glioblastoma has a 5-year survival rate of 9.8%, making it a highly lethal brain tumor.
Glioma stem-like cells are associated with tumor recurrence and resistance to treatment.
MGMT, a DNA repair protein, can reduce the effectiveness of cancer treatments.
Interferon-α/β treatment significantly decreased MGMT levels in glioma cells.
The combination of interferon-α/β and temozolomide improved treatment efficacy compared to temozolomide alone.
Inhibition of NF-κB activity by interferon-α/β may play a role in sensitizing glioma stem-like cells to temozolomide.

AI simplified

Glioma is one of the most common primary tumors of the central nervous system in adults. Glioblastoma (GBM) is the most lethal type of glioma, whose 5-year survival is 9.8% at best. Glioma stem-like cells (GSCs) play an important role in recurrence and treatment resistance. MGMT is a DNA repair protein that removes DNA adducts and therefore attenuates treatment efficiency. It has been reported that interferon-α/β (IFN-α/β) downregulates the level of MGMT and sensitizes glioma cells to temozolomide. In the present study, we assessed whether IFN-α/β is able to sensitize GSCs to temozolomide by modulating MGMT expression. Upon the treatment of IFN-α/β, the efficacy of temozolomide against MGMT‑positive GSCs was markedly enhanced by combination treatment with IFN-α/β when compared with the temozolomide single agent group, and MGMT expression was markedly decreased at the same time. Further mechanistic study showed that IFN-α/β suppressed the NF-κB activity, which further mediated the sensitization of MGMT‑positive GSCs to temozolomide. Our data therefore demonstrated that the application of IFN-α/β is a promising agent with which to enhance temozolomide efficiency and reduce drug resistance, and our findings shed light on improving clinical outcomes and prolonging the survival of patients with malignant gliomas.

Full Text

Full text is available at the source.

View full text ↗

Interferon-α/β enhances temozolomide activity against MGMT-positive glioma stem-like cells

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief