Hsu Fei-Ting, Chang Betty, Chiang I-Tsang, Wu Tai-Hsien, Hwang Jeng-Jong
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Bei-tou, Taipei, Taiwan, R.O.C.
Department of Radiological Technology, Central Taiwan University of Science and Technology, Beitun, Taichung, Taiwan, R.O.C.
In Vivo. 2014 Sep-Oct;28(5):925-33.
BACKGROUND/AIM: Although anticancer effects of sorafenib on renal, liver and colon carcinomas are well-known, its combination effect with ionizing radiation on oral squamous cell carcinoma (OSCC) is unclear. Herein human SAS cells, an OSCC cell line, were used in order to elucidate this combination effect.
Both SAS and SAS/nuclear factor kappa-B-luciferase (SAS/NF-κB-luc2) cell lines were used in the study. Cell viability, NF-κB activation, and protein expression of NF-κB downstream effectors were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, NF-κB-luc2 reporter gene system, NF-κB/DNA binding activity and western blotting.
Sorafenib significantly increased radiation-induced cytotoxicity and apoptosis via both mitochondrial-dependent and independent pathways. In addition, NF-κB activity and downstream effector protein expression induced by radiation was suppressed by sorafenib in SAS/NF-κB-luc2 cells.
Combination of sorafenib with radiation for the treatment of human OSCC shows a synergistic effect via suppression of radiation-induced NF-κB activity and its regulated downstream effector proteins.
背景/目的:尽管索拉非尼对肾癌、肝癌和结肠癌的抗癌作用已为人熟知,但其与电离辐射联合对口腔鳞状细胞癌(OSCC)的作用尚不清楚。因此,本研究使用人OSCC细胞系SAS细胞来阐明这种联合作用。
本研究使用了SAS细胞系和SAS/核因子κB-荧光素酶(SAS/NF-κB-luc2)细胞系。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法、NF-κB-luc2报告基因系统、NF-κB/DNA结合活性检测及蛋白质印迹法分别测定细胞活力、NF-κB激活情况以及NF-κB下游效应蛋白的表达。
索拉非尼通过线粒体依赖和非依赖途径显著增强辐射诱导的细胞毒性和凋亡。此外,在SAS/NF-κB-luc2细胞中,索拉非尼可抑制辐射诱导的NF-κB活性及其下游效应蛋白的表达。
索拉非尼与辐射联合治疗人OSCC通过抑制辐射诱导的NF-κB活性及其调控的下游效应蛋白显示出协同作用。