Hypocretin-1 suppresses malignant progression of glioblastoma cells through Notch1 signaling pathway
Renzheng Huan1, Jianhe Yue1, Jinhai Lan2
1Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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.
Insights
Hypocretin-1, a neuropeptide, effectively inhibits glioblastoma growth, migration, and invasion while promoting apoptosis. This antitumor effect is mediated by suppressing the NOTCH signaling pathway.
Area of Science:
- Neuroscience
- Oncology
- Molecular Biology
Background:
- Hypocretin-1 is a neuropeptide with known antitumor properties against various cancers.
- Its role and mechanism in malignant glioma development remain largely uninvestigated.
Purpose of the Study:
- To investigate the effects of hypocretin-1 on glioblastoma proliferation, apoptosis, migration, and invasion.
- To elucidate the underlying molecular mechanism, focusing on the NOTCH signaling pathway.
Main Methods:
- Assessed hypocretin-1 receptor expression in glioma cell lines and tissues.
- Evaluated hypocretin-1 treatment effects on glioblastoma cell behavior in vitro.
- Measured tumor growth rate and weight in vivo.
- Investigated the role of the NOTCH signaling pathway, including NICD overexpression.
Main Results:
- Hypocretin-1 receptor is expressed in glioma cells and tissues.
- Hypocretin-1 inhibited glioblastoma cell proliferation, migration, and invasion, and induced apoptosis.
- Hypocretin-1 significantly reduced tumor growth rate and weight.
- Hypocretin-1's antitumor effects were mediated by inhibiting the NOTCH signaling pathway, as NICD overexpression reversed these effects.
Conclusions:
- Hypocretin-1 demonstrates significant antitumor activity against glioblastoma.
- The neuropeptide inhibits glioblastoma progression by suppressing the NOTCH signaling pathway.
- Hypocretin-1 holds potential as a therapeutic agent for malignant glioma.
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