期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms24097929
关键词
glioblastoma multiforme; temozolomide; neddylation; combination treatment
There is currently no effective therapy for the increasing incidence of GBM, and TMZ resistance is a major problem. However, combination treatment of MLN4924 and TMZ can decrease cell viability and sensitize TMZ-resistant cells, providing a new treatment strategy for GBM.
There is no effective therapy for the lately increased incidence of glioblastoma multiforme (GBM)-the most common primary brain tumor characterized by a high degree of invasiveness and genetic heterogeneity. Currently, DNA alkylating agent temozolomide (TMZ) is the standard chemotherapy. Nevertheless, TMZ resistance is a major problem in the treatment of GBM due to numerous molecular mechanisms related to DNA damage repair, epigenetic alterations, cellular drug efflux, apoptosis-autophagy, and overactive protein neddylation. Low molecular weight inhibitors of NEDD8-activating enzyme (NAE), such as MLN4924, attenuate protein neddylation and present a promising low-toxicity anticancer agent. The aim of our study was to find an effective combination treatment with TMZ and MLN4924 in our TMZ-resistant GBM cell lines and study the effect of these combination treatments on different protein expressions such as O-6-methylguanine methyltransferase (MGMT) and p53. The combination treatment successfully decreased cell viability and sensitized TMZ-resistant cells to TMZ, foreshadowing a new treatment strategy for GBM.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据