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

Oncology Reports
Dong ShenZhong-ping Chen

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...Continue Reading

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Citations

May 17, 2018·Journal of Neuro-oncology·Adrienn VolakCasey A Maguire
Dec 15, 2017·Neural Regeneration Research·Yao-Dong ZhaoQiang Huang
Jul 19, 2017·CNS Oncology·Gary D LewisBin S Teh
Mar 18, 2020·The Journal of Experimental Medicine·Xiaoyan ZhanJianghong Man
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Nov 23, 2019·Cell Death & Disease·Hai-Ping CaiZhong-Ping Chen
Apr 3, 2020·Science Translational Medicine·Susobhan SarkarV Wee Yong
Oct 20, 2020·Cancer Chemotherapy and Pharmacology·Xiang-Rong NiZhong-Ping Chen
Aug 3, 2021·Frontiers in Cell and Developmental Biology·Quan ChengZhiwei Xia
Jul 31, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Mingjie QingLijuan Cheng

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