Faculty of Medicine, Department of Medical Biology, Ege University, Bornova, Izmir, Turkey.
J Cell Biochem. 2019 Jan;120(1):380-395. doi: 10.1002/jcb.27393. Epub 2018 Aug 26.
The effect of Wnt pathway in head and neck cancer could not be elucidated, even though the aberrant Wnt signaling plays a key role in the development of many types of cancer. The inhibitor of β-catenin responsive transcription (ICRT-3) blocks the Wnt signaling pathway by binding to β-catenin, which is a coactivator of the Wnt signaling pathway and a promising agent for inhibiting aberrant signaling. In our study, we aimed to evaluate the effect of ICRT-3 on the cytotoxicity, apoptosis, cell cycle progression, migration, and gene expressions in head and neck cancer stem cell (HNCSC) and hypopharynx cancer. The effect of this compound on cytotoxicity and cell viability in FaDu and HNCSC line was assessed by using the water-soluble tetrazolium salt-1 method. The effect of ICRT-3 on apoptosis was detected by using Annexin V and caspase-3, caspase-9 kit, on cell cycle progression by cycle test plus DNA reagent kit, on gene expression by dual luciferase reporter assay, and on migration activity by wound healing assay in both cell lines. ICRT-3 was determined to have cytotoxic and apoptotic effect in both cell lines. In addition, it was also found that the administration of ICRT-3 caused cell cycle arrest and significant decrease in gene expression level and migration ability of the cells.
尽管异常的 Wnt 信号在许多类型的癌症的发展中起着关键作用，但 Wnt 通路在头颈部癌症中的作用仍不清楚。β-连环蛋白反应转录抑制剂 (ICRT-3) 通过与 Wnt 信号通路的共激活因子β-连环蛋白结合来阻断 Wnt 信号通路，这是一种有前途的抑制异常信号的药物。在我们的研究中，我们旨在评估 ICRT-3 对口腔癌和下咽癌细胞中的头颈部癌症干细胞 (HNCSC) 的细胞毒性、细胞凋亡、细胞周期进程、迁移和基因表达的影响。通过使用水溶性四唑盐-1 法评估该化合物对 FaDu 和 HNCSC 系的细胞毒性和细胞活力的影响。通过 Annexin V 和 caspase-3、caspase-9 试剂盒检测 ICRT-3 对细胞凋亡的影响，通过细胞周期检测试剂盒加 DNA 试剂检测细胞周期进程，通过双荧光素酶报告基因检测检测基因表达，通过划痕愈合试验检测迁移活性在这两种细胞系中。结果表明，ICRT-3 对两种细胞系均具有细胞毒性和促凋亡作用。此外，还发现 ICRT-3 的给药导致细胞周期停滞和细胞基因表达水平和迁移能力显著下降。
