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

Abstract

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.

• Authors: Dong Shen, Cheng-Cheng Guo, Jing Wang, Zhi-Kun Qiu, Ke Sai, Qun-Ying Yang, Yin-Sheng Chen, Fu-Rong Chen, Jie Wang, Lawrence Panasci, Zhong-Ping Chen
• Journal: Oncology reports (Oncol Rep) Vol. 34 Issue 5 Pg. 2715-21 (Nov 2015) ISSN: 1791-2431 [Electronic] Greece
• PMID: 26329778 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Interferon Type I
• Tumor Suppressor Proteins
• Dacarbazine
• DNA Modification Methylases
• MGMT protein, human
• DNA Repair Enzymes
• Temozolomide

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, pharmacology)
• Brain Neoplasms (drug therapy, genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA Modification Methylases (genetics, metabolism)
• DNA Repair Enzymes (genetics, metabolism)
• Dacarbazine (administration & dosage, analogs & derivatives, pharmacology)
• Drug Synergism
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioma (drug therapy, genetics, metabolism, pathology)
• Humans
• Interferon Type I (administration & dosage, pharmacology)
• Male
• Mice
• Neoplastic Stem Cells (drug effects)
• Temozolomide
• Tumor Suppressor Proteins (genetics, metabolism)
• Xenograft Model Antitumor Assays