Li Jiansen, Zheng Xiangqian, Gao Ming, Zhao Jingzhu, Li Yigong, Meng Xiangrui, Qian Biyun, Li Jiafeng
Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin National Clinical Research Center for Cancer, Tianjin 300060, P.R. China.
Oncol Rep. 2017 Jan;37(1):458-464. doi: 10.3892/or.2016.5281. Epub 2016 Nov 29.
Anaplastic thyroid cancer (ATC), usually derived from well-differentiated thyroid cancers is one of the most lethal human endocrine malignancies. In the present study, we report that in human ATC tumor tissue samples exist undetectable Notch1 and the active Notch1 intracellular domain could not be detected in ATC-CAL-62 cells. Interesting, suberoyl bis-hydroxamic acid (SBHA) administration could induce Notch1 intracellular domain levels in a dose-dependent manner, coupled with the increase of p53 and p21. Furthermore, ectopic expression of Notch1 or deletion of p53 with small-interfering RNA was able to abolish the effects of SBHA to elevation of Notch1 and p53 in ATC cells. As a result, SBHA treatment efficiently induced ATC cell apoptosis. These results indicate that SBHA may play antitumor functions via regulating Notch1/p53 signals, and highlight that SBHA could have clinical potential to benefit the therapy of ATC patients.
间变性甲状腺癌（ATC）通常起源于高分化甲状腺癌，是人类最致命的内分泌恶性肿瘤之一。在本研究中，我们报告在人类ATC肿瘤组织样本中存在无法检测到的Notch1，并且在ATC - CAL - 62细胞中无法检测到活性Notch1细胞内结构域。有趣的是，施用辛二酰双羟肟酸（SBHA）能够以剂量依赖的方式诱导Notch1细胞内结构域水平升高，同时伴随着p53和p21的增加。此外，Notch1的异位表达或用小干扰RNA缺失p53能够消除SBHA对ATC细胞中Notch1和p53升高的影响。结果，SBHA处理有效地诱导了ATC细胞凋亡。这些结果表明，SBHA可能通过调节Notch1/p53信号发挥抗肿瘤作用，并突出表明SBHA可能具有临床潜力，使ATC患者受益于治疗。
