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Prucalopride inhibits the glioma cells proliferation and induces autophagy via AKT-mTOR pathway.
- Source :
-
BMC Neurology . 6/4/2018, Vol. 18 Issue 1, pN.PAG-N.PAG. 1p. 5 Graphs. - Publication Year :
- 2018
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Abstract
- <bold>Backgrounds: </bold>Glioma is the most fatal primary brain glioma in central nervous system mainly attributed to its high invasion. Prucalopride, a Serotonin-4 (5-HT4) receptor agonist, has been reported to regulate neurodevelopment. This study aimed to investigate the influence of the Prucalopride on glioma cells and unveil underlying mechanism.<bold>Methods: </bold>In this study, glioma cells proliferation was evaluated by Cell counting kit-8 (CCK8). Wound healing and transwell assay were used to test cellular migration and invasion. Flow cytometry was utilized to determine cellular apoptosis rate. Apoptosis related markers, autophagy markers, and protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway key molecules were detected using western blot assay.<bold>Results: </bold>As a result, the proliferation, migration and invasiveness of glioma cells were impaired by Prucalopride treatment, the apoptosis rate of glioma cells was enhanced by Prucalopride stimulation, accompanied by the increased pro-apoptosis proteins Bax and Cleaved caspase-3 and decreased anti-apoptosis protein Bcl-2. Prucalopride significantly promoted autophagy by increased expression level of Beclin 1 and LC3-II, while decreased expression level of p62. Prucalopride administration resulted in obvious inhibitions of key molecules of AKT-mTOR pathway, including phosphorylated- (p-) AKT, p-mTOR and phosphorylated-ribosomal p70S6 kinase (p-P70S6K).<bold>Conclusions: </bold>Taking together, these results indicate that Prucalopride may be likely to play an anti-tumor role in glioma cells, which suggests potential implications for glioma promising therapy alternation in the further clinics. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GLIOMAS
*CELL proliferation
*AUTOPHAGY
*PROTEIN kinase B
*MTOR protein
*RAPAMYCIN
Subjects
Details
- Language :
- English
- ISSN :
- 14712377
- Volume :
- 18
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- BMC Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 129966513
- Full Text :
- https://doi.org/10.1186/s12883-018-1083-7