期刊
ONCOLOGY REPORTS
卷 45, 期 5, 页码 -出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2021.8025
关键词
glioblastoma; apoptosis; tumorigenesis; calpain; endoplasmic reticulum stress; mitochondrial dysfunction
类别
资金
- National Natural Science Foundation of China (NSFC) [81430021, 81771521]
This study investigated the antineoplastic effect and pathways of action of dopamine receptor D1 agonist SKF83959 on GBM cells. The results showed that SKF83959 induced apoptotic cell death in GBM cells through mechanisms such as increasing intracellular calcium levels and oxidative stress. These findings suggest a potential therapeutic target for human GBM treatment by regulating calpain expression and activity.
Recent studies have reported the important roles of dopamine receptors in the early development and progression of glioblastoma (GBM). The present research aimed to explore the antineoplastic effect and intrinsic pathways of action of dopamine receptor D1 agonist SKF83959 on GBM cells. Flow cytometric analysis revealed a significant level of apoptotic cell death under SKF83959 treatment. SKF83959 administration increased intracellular calcium levels and oxidative stress through the phospholipase C/inositol trisphosphate pathway. The downstream calpains were activated and dysregulated by the increased calcium levels. The mitochondrial membrane potential-dependent staining assay revealed decreased mitochondrial transmembrane potential in GBM cells under SKF83959 treatment. The mitochondrial/cytosolic fraction and western blotting further demonstrated mitochondrial dysfunction and endoplasmic reticulum stress, followed by apoptosis. The calpain inhibitor, calpastatin, significantly reversed the increase in mitochondrial injury and endoplasmic reticulum stress and eventually ameliorated GBM cell apoptosis during SKF83959 treatment. Finally, the in vivo inhibitory efficacy of SKF83959 was verified in GBM xenograft models. In addition, immunohistochemistry and western blotting both revealed increased expression of calpains in xenograft GBM tissues. These results suggested a potential therapeutic target for human GBM treatment regarding calpain expression and activity regulation.
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