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

Brain Res Bull. 2023 May:196:46-58. doi: 10.1016/j.brainresbull.2023.03.006. Epub 2023 Mar 15.

Abstract

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.

Keywords: Glioblastoma; Hypocretin-1; Malignant progression; Notch signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Glioblastoma* / pathology
  • Glioma*
  • Humans
  • Male
  • Orexins / pharmacology
  • Receptor, Notch1 / metabolism
  • Signal Transduction

Substances

  • Orexins
  • Receptor, Notch1
  • NOTCH1 protein, human