Department of Neurosurgery, Tianjin Huanhu Hospital.
Department of Pathology, Tianjin Huanhu Hospital.
Tohoku J Exp Med. 2024 Sep 18;263(3):199-210. doi: 10.1620/tjem.2024.J033. Epub 2024 May 24.
Glioblastoma (GBM) is a malignant primary brain tumor and an essential contributor to morbidity and mortality globally. Arsenic trioxide (ATO) exerts specific roles in preventing tumor growth. This study investigated the role of ATO in GBM cell behaviors and stemness. The effects of ATO on the malignant behavior of GBM cells, tumor stemness, and epithelial-mesenchymal transition (EMT) factors in mouse tumor tissues were explored. Targets of ATO in GBM were predicted using multiple databases. Subsequently, the expression of retinoic acid-related orphan receptor beta (RORB), WNT-1, β-Catenin, and c-Myc expression were examined in GBM cells before and after ATO treatment.ATO inhibited the malignant behavior of GBM cells in vitro and slowed down the GBM growth in vivo by inhibiting the stemness. The inhibitory effect of ATO on GBM was achieved by promoting RORB levels and strengthening the antagonism to β-Catenin to inhibit Wnt signaling, thus inhibiting tumor growth. Collectively, ATO induced RORB levels in GBM cells and strengthened the antagonistic effect on β-Catenin, thus inhibiting WNT signaling and tumor growth.
胶质母细胞瘤（GBM）是一种恶性原发性脑肿瘤，也是全球发病率和死亡率的重要原因。三氧化二砷（ATO）在抑制肿瘤生长方面发挥着特定的作用。本研究探讨了 ATO 在 GBM 细胞行为和干细胞特性中的作用。研究了 ATO 对小鼠肿瘤组织中 GBM 细胞恶性行为、肿瘤干细胞特性和上皮间质转化（EMT）因子的影响。使用多个数据库预测了 ATO 在 GBM 中的作用靶点。然后，在 ATO 处理前后检测了 GBM 细胞中维甲酸相关孤儿受体β（RORβ）、WNT-1、β-连环蛋白和 c-Myc 的表达。ATO 通过抑制干细胞特性来抑制体外 GBM 细胞的恶性行为，并减缓体内 GBM 的生长。ATO 对 GBM 的抑制作用是通过促进 RORβ 水平和加强对β-连环蛋白的拮抗作用来抑制 Wnt 信号通路，从而抑制肿瘤生长。总之，ATO 诱导 GBM 细胞中 RORβ 水平的升高，并加强对β-连环蛋白的拮抗作用，从而抑制 WNT 信号通路和肿瘤生长。
