Xu Jiayun, Sun Shanshan, Zhang Wei, Dong Jianhong, Huang Changgang, Wang Xin, Jia Mengxian, Yang Hao, Wang Yongjie, Jiang Yuanyuan, Cao Liying, Huang Zhihui
College of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Front Pharmacol. 2022 Nov 30;13:1027577. doi: 10.3389/fphar.2022.1027577. eCollection 2022.
Glioblastoma (GBM) is the most malignant glioma in brain tumors with low survival and high recurrence rate. Irigenin, as an isoflavone compound extracted from Shegan, has shown many pharmacological functions such as antioxidant, anti-inflammatory and anti-tumor. However, the effects of irigenin on GBM cells and the related molecular mechanisms remain unexplored. In this study, we found that irigenin inhibited the proliferation of GBM cells in a dose-dependent manner by several assays . Subsequently, we found that irigenin arrested cell cycle at G2/M phase and induced apoptosis of GBM cells . In addition, irigenin inhibited the migration of GBM cells. Mechanically, we found that irigenin treatment decreased the expression of YAP (yes-associated protein), suppressed β-catenin signaling. Furthermore, overexpression of YAP partially restored the anti-tumor effects of irigenin on GBM cells . Finally, we found that irigenin inhibited the growth of tumor in GBM xenograft mice model through inactivation of YAP. Taken together, these results suggest that irigenin exerts its anticancer effects on GBM inhibiting YAP/β-catenin signaling, which may provide a new strategy for the treatment of GBM.
胶质母细胞瘤(GBM)是脑肿瘤中最恶性的胶质瘤,生存率低且复发率高。鸢尾黄素作为从射干中提取的一种异黄酮化合物,已显示出许多药理功能,如抗氧化、抗炎和抗肿瘤。然而,鸢尾黄素对GBM细胞的作用及其相关分子机制仍未被探索。在本研究中,我们通过多种实验发现鸢尾黄素以剂量依赖的方式抑制GBM细胞的增殖。随后,我们发现鸢尾黄素使细胞周期停滞在G2/M期并诱导GBM细胞凋亡。此外,鸢尾黄素抑制GBM细胞的迁移。机制上,我们发现鸢尾黄素处理降低了YAP(Yes相关蛋白)的表达,抑制了β-连环蛋白信号传导。此外,YAP的过表达部分恢复了鸢尾黄素对GBM细胞的抗肿瘤作用。最后,我们发现鸢尾黄素通过使YAP失活抑制GBM异种移植小鼠模型中的肿瘤生长。综上所述,这些结果表明鸢尾黄素通过抑制YAP/β-连环蛋白信号传导对GBM发挥抗癌作用,这可能为GBM的治疗提供一种新策略。