期刊
CHEMICAL BIOLOGY & DRUG DESIGN
卷 92, 期 1, 页码 1344-1356出版社
WILEY
DOI: 10.1111/cbdd.13199
关键词
-emitter (225)AcDOTA-substance P biomolecule; glioblastoma cells; glioblastoma stem cells; targeted alpha therapy; temozolomide
Glioblastoma multiforme (GBM) is the most malignant form of brain tumors with dismal prognosis despite treatment by surgery combined with radiotherapy and chemotherapy. The neuropeptide Substance P (SP) is the physiological ligand of the neurokinin-1 receptor, which is highly expressed in glioblastoma cells. Thus, SP represents a potential ligand for targeted alpha therapy. In this study, a protocol for the synthesis of SP labeled with the alpha emitter Ac-225 was developed and binding affinity properties were determined. The effects of Ac-225-DOTA-SP were investigated on human glioblastoma cell lines (T98G, U87MG, U138MG) as well as GBM stem cells. A significant dose-dependent reduction in cell viability was detected up to 6days after treatment. Also, colony-forming capacity was inhibited at the lower doses tested. In comparison, treatment with the conventional agent temozolomide showed higher cell viability and colony-forming capacity. Ac-225-DOTA-SP treatment caused induction of late apoptosis pathways. Cells were arrested to G2/M-phase upon treatment. Increasing doses and treatment time caused additional S-phase arrest. Similar results were obtained using human glioblastoma stem cells, known to show radioresistance. Our data suggest that Ac-225-DOTA-SP is a promising compound for treatment of 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