Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 109, Issue -, Pages 1032-1040Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.10.122
Keywords
Glioma; Neferine; microRNA-10b; Proliferation; PTEN/PI3K/AKT; p38MAPK
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Background: Glioma is a common brain tumor, which is a serious threat to the life and health of human with high mortality rate. Recently, neferine (NEF) has been reported to play an important role in various cancers. In the study, we aimed to investigate the effect of NEF on human glioma cell line U251. Methods: U251 cells were pre-treated with different concentrations of NEF, and then CCK-8, BrdU, flow cytometry and transwell assays were used to test cell proliferation, apoptosis, migration and invasion. Subsequently, the expression vectors of miR-10b mimic and miR-10b inhibitor were transfected into U251 cells, and the relative expression of miR-10b was examined by qRT-PCR. The main proteins of CyclinD1/p53/p16, pro-Caspase-3/-9, cleaved-Caspase-3/-9, MMP-9, Vimentin, PTEN/PI3K/AKT and p38MAPK signal pathways were determined by western blot assay. Results: NEF significantly suppressed cell proliferation, and induced apoptosis, as well as regulated CyclinD1, p53, p16 and cleaved-Caspase-3/-9 expressions in U251 cells. Moreover, NEF inhibited cell migration, invasion and decreased MMP-9 and Vimentin expression in U251 cells. Additionally, miR-10b expression was downregulated in NEF-stimulated cells, and overexpression of miR-10b reversed the regulatory effects of NEF on U251 cells proliferation, migration, invasion and apoptosis. Additionally, we found that PTEN was a direct target of miR-10b in U251 cells. Besides, NEF deactivated PTEN/PI3K/AKT and p38MAPK signal pathways by downregulation of miR-10b in U251 cells. Conclusions: These results suggested that NEF exerted anti-tumor effect by down-regulation of miR-10b and deactivation of PTEN/PI3K/AKT and p38MAPK signal pathways in glioma cells. These findings might provide a novel therapeutic strategy for glioma.
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