Hypocretin-1通过Notch1信号通路抑制恶性胶质母细胞瘤的进展。
Hypocretin-1 suppresses malignant progression of glioblastoma cells through Notch1 signaling pathway.
发表日期:2023 Mar 14
作者:
Renzheng Huan, Jianhe Yue, Jinhai Lan, Jia Wang, Yuan Cheng, Jiqin Zhang, Ying Tan
来源:
Brain Structure & Function
摘要:
Hypocretin-1是一种多功能的神经肽,已被鉴定为可能的抗肿瘤剂,因其在抑制肿瘤生长,包括结肠癌、神经内分泌肿瘤和前列腺癌中的作用而闻名。然而,Hypocretin-1在恶性胶质瘤的发生和发展中的作用和机制尚未得到很好的研究。因此,我们研究了Hypocretin-1对胶质母细胞瘤增殖、凋亡、迁移和侵袭及其机制的影响。我们发现,Hypocretin-1受体在胶质瘤细胞系和胶质瘤组织中均有表达。 Hypocretin-1治疗可以抑制胶质母细胞瘤细胞的增殖、迁移和侵袭,诱导细胞凋亡。同时,Hypocretin-1治疗显著降低肿瘤生长速度和肿瘤重量。此外,机制研究发现,Hypocretin-1通过抑制NOTCH信号通路发挥抗肿瘤作用。 NICD的过表达显著逆转了Hypocretin对胶质母细胞瘤的抗肿瘤作用。综上所述,这些发现表明,Hypocretin-1通过NOTCH信号通路在体内外抑制胶质母细胞瘤的增殖、迁移和侵袭并诱导凋亡。 版权所有 © 2023 Elsevier Inc. 发布。
Hypocretin-1 is a multifunctional neuropeptide that has been identified as a potential antitumor agent for its role in inhibiting tumor growth, including in colon cancer, neuroendocrine tumor, and prostate cancer. However, the role and mechanism of hypocretin-1 in the occurrence and development of malignant glioma have not been well studied. Therefore, we investigated the effect of hypocretin-1 on glioblastoma proliferation, apoptosis, migration and invasion and its mechanism. We found that the hypocretin-1 receptor was expressed in both glioma cell lines and glioma tissues. Hypocretin-1 treatment can inhibit glioblastoma cell proliferation, migration and invasion, and induce cell apoptosis. Meanwhile, hypocretin-1 treatment significantly reduces tumor growth rate and tumor weight. In addition, mechanistic studies have found that hypocretin-1 exerts antitumor effects by inhibiting NOTCH signaling pathway. Overexpression of NICD significantly reversed the antitumor effect of hypocretin on glioblastoma. Taken together, these findings suggest that hypocretin-1 inhibits glioblastoma proliferation, migration and invasion and induces apoptosis in vitro and in vivo through NOTCH signaling pathway.Copyright © 2023. Published by Elsevier Inc.