Exendin-4 inhibits glioma cell migration, invasion and epithelial-to-mesenchymal transition through GLP-1R/sirt3 pathway

[Display omitted] •GLP-1R was expressed in all glioma cell lines.•Exendin-4 inhibited glioma cell survival and proliferation.•Exendin-4 suppressed glioma cell migration, invasion and EMT.•Exendin-4 elevated sirt3 expression.•Depletion the level of GLP-1R or sirt3 both reversed the effects of exendin...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2018-10, Vol.106, p.1364-1369
Main Authors: Nie, Zhi-Jun, Zhang, Yin-Gang, Chang, Yan-Hai, Li, Quan-Yi, Zhang, Yue-Lin
Format: Article
Language:English
Subjects:
Exendin-4
Glioblastoma
GLP-1R
Sirt3
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Summary:[Display omitted] •GLP-1R was expressed in all glioma cell lines.•Exendin-4 inhibited glioma cell survival and proliferation.•Exendin-4 suppressed glioma cell migration, invasion and EMT.•Exendin-4 elevated sirt3 expression.•Depletion the level of GLP-1R or sirt3 both reversed the effects of exendin-4. GLP-1 analogue exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist which shares 53% sequence with GLP-1, plays an essential role in human tumors. However, the function and mechanisms underlying the effects of exendin-4 on glioma cell migration, invasion and epithelial-to-mesenchymal transition are still obscure. Firstly, we demonstrated that GLP-1R was expressed in all glioma cell lines including U87, U251, U373 and A172. Exendin-4 treatment inhibited glioma cell survival, proliferation, migration and invasion. Also, exendin-4 inhibited epithelial-to-mesenchymal transition through positively regulating the expression of E-cadherin (epithelial marker), and negatively regulating the level of Vimentin (mesenchymal marker). Interestingly, we next demonstrated that exendin-4 elevated sirt3 expression dependent on the high level of GLP-1R in U87 and 251 cells. Finally, we confirmed that depletion the level of GLP-1R or sirt3 both reversed the inhibitory action of exendin-4 on glioma cell migration and invasion. These findings demonstrate that exendin-4 treatment suppressed the migration and invasion of glioma cells through GLP-1R/sirt3 pathway and exendin-4 plays an inhibitory effect on glioblastoma cell migration and invasion.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2018.07.092