Division of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79, Qingchun Road, Hangzhou, Zhejiang Province, China.
Mol Biol Rep. 2022 Aug;49(8):7507-7519. doi: 10.1007/s11033-022-07559-y. Epub 2022 May 27.
Glioma is the most common malignant brain tumor in adults. The effects of conventional treatment regimens are still limited to prolonging the survival of patients. Histone deacetylases (HDACs) are potential targets for tumor treatment. Pracinostat is a new type of HDAC inhibitor (HDACi) that has a significant antitumor effect on a variety of tumors. Thus, we aim to investigate the role of pracinostat in human glioma and explored its underlying mechanism.
Cell viability, proliferation and apoptosis of human glioma cell lines were measured by Cell Counting kit 8 and flow cytometry. Pathway verification and protein interaction were determined by quantitative real-time polymerase chain reaction, Western blotting and immunofluorescence staining. Transwell technology was used to assess the migration and invasion of cells. Clinical significance of TIMP3, MMP9 and MMP2 in glioma was analyzed through The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database.
Functionally, pracinostat not only inhibited proliferation and induced apoptosis but also inhibited migration and invasion in human glioma cell lines. Mechanistically, pracinostat increased the expression of TIMP3 and decreased the expression of MMP2, MMP9 and VEGF in human glioma cells in vitro and in vivo. In addition, pracinostat inhibited both the PI3K/Akt signaling pathway and the STAT3 pathway.
Our results strongly support the potential clinical use of pracinostat as a novel therapy for human glioma in the near future.
神经胶质瘤是成年人中最常见的恶性脑肿瘤。常规治疗方案的效果仍然仅限于延长患者的生存时间。组蛋白去乙酰化酶（HDACs）是肿瘤治疗的潜在靶点。普拉西诺司他是一种新型的 HDAC 抑制剂（HDACi），对多种肿瘤具有显著的抗肿瘤作用。因此，我们旨在研究普拉西诺司他在人类神经胶质瘤中的作用，并探讨其潜在机制。
通过细胞计数试剂盒 8 和流式细胞术测量人神经胶质瘤细胞系的细胞活力、增殖和凋亡。通过定量实时聚合酶链反应、Western blot 和免疫荧光染色确定途径验证和蛋白相互作用。Transwell 技术用于评估细胞的迁移和侵袭。通过癌症基因组图谱（TCGA）数据库和基因型组织表达（GTEx）数据库分析 TIMP3、MMP9 和 MMP2 在神经胶质瘤中的临床意义。
功能上，普拉西诺司他不仅抑制增殖并诱导凋亡，而且还抑制人神经胶质瘤细胞系的迁移和侵袭。在体外和体内，普拉西诺司他增加了 TIMP3 的表达，降低了 MMP2、MMP9 和 VEGF 的表达。此外，普拉西诺司他抑制了 PI3K/Akt 信号通路和 STAT3 通路。
我们的结果强烈支持在不久的将来将普拉西诺司他作为人类神经胶质瘤的新型治疗方法的临床应用潜力。
