Dataset Information

Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-?B Signaling Pathway.

ABSTRACT: Invasion and metastasis of glioblastoma-initiating cells (GICs) are thought to be responsible for the progression and recurrence of glioblastoma multiforme (GBM). A safe drug that can be applied during the rest period of temozolomide (TMZ) maintenance cycles would greatly improve the prognosis of GBM patients by inhibiting GIC invasion. Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines. The current study aimed to evaluate whether RES can inhibit GIC invasion in vitro and in vivo. GICs were identified using CD133 and Nestin immunofluorescence staining and tumorigenesis in non-obese diabetic severe combined immunodeficient (NOD/SCID) mice. Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo. The activity of matrix metalloproteinases (MMPs) was measured by the gelatin zymography assay. Western blotting analysis and immunofluorescence staining were used to determine the expression of signaling effectors in GICs. We demonstrated that RES suppressed the adhesion, invasion and migration of GICs in vitro and in vivo. Moreover, we proved that RES inhibited the invasion of GICs via the inhibition of PI3K/Akt/NF-?B signal transduction and the subsequent suppression of MMP-2 expression.

SUBMITTER: Jiao Y

PROVIDER: S-EPMC4488790 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-κB Signaling Pathway.

Jiao Yuming Y Li Hao H Liu Yaodong Y Guo Anchen A Xu Xiaoxue X Qu Xianjun X Wang Shuo S Zhao Jizong J Li Ye Y Cao Yong Y

Nutrients 20150602 6

Invasion and metastasis of glioblastoma-initiating cells (GICs) are thought to be responsible for the progression and recurrence of glioblastoma multiforme (GBM). A safe drug that can be applied during the rest period of temozolomide (TMZ) maintenance cycles would greatly improve the prognosis of GBM patients by inhibiting GIC invasion. Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines. The current study aimed to evaluate whether RES can ...[more]

PMID: 26043036

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Project description:PurposeNectin-4 is specifically up-regulated in various tumors, exert crucial effects on tumor occurrence and development. Nevertheless, the role and molecular mechanism of Nectin-4 in osteosarcoma (OS) are rarely studied.MethodsThe expression of Nectin-4 and its relationship with clinical characteristics of OS were investigated using OS clinical tissues, tissue microarrays, TCGA, and GEO databases. Moreover, the effect of Nectin-4 on cell growth and mobility was detected by CCK-8, colony formation, transwell, and wound-healing assays. The RT-qPCR, Western blotting, and luciferase reporter assays were performed to explore molecular mechanisms through which Nectin-4 mediates the expression of miR-520c-3p, thus modulating PI3K/AKT/NF-κB signaling. In vivo mice models constructed by subcutaneous transplantation and tail vein injection were used to validate the functional roles of Nectin-4 and miR-520c-3p.ResultsNectin-4 displayed a higher expression in OS tumor tissues compared with normal tissues, and its overexpression was positively associated with tumor stage and metastasis in OS patients. Functionally, Nectin-4 enhanced OS cells growth and mobility in vitro. Mechanistically, Nectin-4 down-regulated the levels of miR-520c-3p that directly targeted AKT-1 and P65, thus leading to the stimulation of PI3K/AKT/NF-κB signaling. In addition, the expression of miR-520c-3p was apparently lower in OS tissues than in normal tissues, and its low expression was significantly related to tumor metastasis. Furthermore, ectopic expression of miR-520c-3p markedly blocked the effect of Nectin-4 on OS cell growth and mobility. Knockdown of Nectin-4 could suppress the tumorigenesis and metastasis in vivo, which could be remarkably reversed by miR-520c-3p silencing.ConclusionsNectin-4 as an oncogene can promote OS progression and metastasis by activating PI3K/AKT/NF-κB signaling via down-regulation of miR-520c-3p, which could represent a novel avenue for identifying a potential therapeutic target for improving patient outcomes.

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Dataset Information

Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-?B Signaling Pathway.

Publications

Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-κB Signaling Pathway.

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