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瑞戈非尼诱导人膀胱癌细胞凋亡并抑制其转移潜能。

Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells.

作者信息

Hsu Fei-Ting, Sun Cho-Chin, Wu Chia-Hsing, Lee Yen-Ju, Chiang Chih-Hung, Wang Wei-Shu

机构信息

Department of Radiology, School of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.

Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.

出版信息

Anticancer Res. 2017 Sep;37(9):4919-4926. doi: 10.21873/anticanres.11901.

Abstract

The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro.

摘要

本研究的目的是在体外验证瑞戈非尼对TSGH 8301人膀胱癌细胞凋亡和转移潜能的影响。用不同浓度的瑞戈非尼处理细胞不同时间。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法、流式细胞术、细胞迁移和侵袭试验以及蛋白质印迹法评估瑞戈非尼对细胞活力、凋亡途径、转移潜能以及转移和抗凋亡蛋白表达的影响。我们发现瑞戈非尼显著降低细胞活力、细胞迁移和侵袭以及转移和抗凋亡蛋白的表达。此外,瑞戈非尼显著诱导亚G期细胞积累、线粒体膜电位丧失以及活性半胱天冬酶-3和半胱天冬酶-8的表达。这些结果表明,瑞戈非尼不仅诱导凋亡,而且在体外抑制膀胱癌细胞TSGH 8301的转移潜能。

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