Hypocretin-1 suppresses malignant progression of glioblastoma cells through Notch1 signaling pathway

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.