Hu Sunkuan, Chen Qiuxiang, Lin Tiesu, Hong Wandong, Wu Wenzhi, Wu Ming, Du Xiaojing, Jin Rong
Department of Digestive Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Lett. 2018 May;15(5):6171-6178. doi: 10.3892/ol.2018.8118. Epub 2018 Feb 26.
Due to the complex function of the Notch signal pathway in gastric cancer (GC), the association between Notch homolog 1 (Notch1) intracellular domain (NICD) and differentiation of GC remains unknown. The present study aimed to investigate the potential association between NICD and GC differentiation, and demonstrated that poorly differentiated GC expressed increased NICD levels compared with well differentiated GC. A γ-secretase inhibitor inhibited the growth of AGS cells through downregulating NICD level. Additional data suggested that a COX-2 inhibitor caused a marked reduction of NICD level in comparison with a control group treated with dimethyl sulfoxide. Combined administration of γ-secretase and COX-2 inhibitor produced a marked inhibition of growth in AGS cells, which suggests that patients with poorly differentiated GC may benefit from the blockage of NICD, which potentially serves a role in GC differentiation.
由于Notch信号通路在胃癌（GC）中具有复杂的功能，Notch同源物1（Notch1）胞内结构域（NICD）与GC分化之间的关联仍不清楚。本研究旨在探讨NICD与GC分化之间的潜在关联，并证明与高分化GC相比，低分化GC表达的NICD水平升高。一种γ-分泌酶抑制剂通过下调NICD水平抑制AGS细胞的生长。额外的数据表明，与用二甲基亚砜处理的对照组相比，一种COX-2抑制剂导致NICD水平显著降低。联合使用γ-分泌酶和COX-2抑制剂对AGS细胞的生长产生了显著抑制作用，这表明低分化GC患者可能从阻断NICD中获益，NICD可能在GC分化中起作用。
