Department of Biomedical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, Netherlands.
Zonula Incorporated, Kirkland, Quebec, H9J 2X2, Canada.
Biochem Biophys Res Commun. 2020 Aug 20;529(2):162-168. doi: 10.1016/j.bbrc.2020.06.001. Epub 2020 Jun 22.
Glioblastoma multiforme (GBM) is a deadly type of brain cancer. There is a need to identify novel therapies for GBM as current treatments only marginally increase survival. Modelling the complexity of cancerous tissues using 3D bioprinted constructs serves as a novel approach for preclinical testing of anticancer drugs. A novel small molecule antagonist of the cell adhesion molecule, N-cadherin (NCAD), (S)-1-(3,4-Dichlorophenoxy)-3-(4-((S)-2-hydroxy-3-(4-methoxyphenoxy)propylamino)piperidin-1-yl)propan-2-ol has shown promise as an anticancer agent. This study investigated the influence of this antagonist on GBM cells bioprinted with astrocytes into 3D constructs. The NCAD antagonist prevented spheroid formation and induced cell death in the 3D model. This is the first demonstration that an NCAD antagonist can cause GBM cell death.
多形性胶质母细胞瘤（GBM）是一种致命的脑癌。由于目前的治疗方法只能略微延长患者的生存时间，因此需要寻找新的治疗方法。使用 3D 生物打印构建体模拟癌症组织的复杂性是一种用于临床前测试抗癌药物的新方法。一种新型的细胞黏附分子 N-钙黏蛋白（NCAD）的小分子拮抗剂（S）-1-（3,4-二氯苯氧基）-3-（4-（（S）-2-羟基-3-（4-甲氧基苯氧基）丙基氨基）哌啶-1-基）丙烷-2-醇已显示出作为抗癌药物的潜力。本研究调查了该拮抗剂对与星形胶质细胞共生物打印到 3D 构建体中的 GBM 细胞的影响。NCAD 拮抗剂阻止了球体的形成并诱导了 3D 模型中的细胞死亡。这是首次证明 NCAD 拮抗剂可导致 GBM 细胞死亡。
