4.4 Article

SMAC Mimetic/IAP Inhibitor Birinapant Enhances Radiosensitivity of Glioblastoma Multiforme

期刊

RADIATION RESEARCH
卷 195, 期 6, 页码 549-560

出版社

RADIATION RESEARCH SOC
DOI: 10.1667/RADE-20-00171.1

关键词

-

向作者/读者索取更多资源

Research has shown that birinapant can enhance the radiosensitivity of glioblastoma cell lines, with particularly significant effects observed in the U-251 cell line. The combination treatment of birinapant and radiation therapy demonstrated tumor growth delay and a survival benefit in both in vitro and in vivo models, warranting further investigation into this potential treatment approach.
Birinapant is a novel SMAC peptidomimetic molecule in clinical development. It suppresses the inhibitor of apoptosis proteins (IAPs) and promotes cytochrome-C/Apaf-1/caspase-9 activation to induce effective apoptosis. Because IAP inhibition has been shown to enhance the sensitivity of cancer cells to radiation, we investigated the role of birinapant in radiosensitization of glioblastoma cells in vitro and in vivo. Two glioblastoma cell lines, U-251 and U-87, were used to analyze radiosensitization in vitro with 7-AAD cell death/apoptosis and clonogenic assays. Subcutaneous flank (U-251 and U-87) and intracranial orthotopic (U-251) xenografts in nude mice were used to evaluate radiosensitization in vivo. TNF-alpha levels in media and serum were measured using electrochemiluminescence. Radiosensitization in vitro was more prominent for U-251 cells than for U-87 cells. In vivo, in both tumor models, significant tumor growth delay was observed with combination treatment compared to radiation alone. There was a survival benefit with combination treatment in the orthotopic U-251 model. TNF-alpha levels in media correlated directly with radiation dose in vitro. These findings show that birinapant can enhance the radiosensitivity of glioblastoma cell lines in cell-based assays and tumor models via radiation-induced TNF-alpha. Further study into the use of birinapant with radiation therapy is warranted. (C) 2021 by Radiation Research Society

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。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据