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Nutrients 2015, 7(6), 4383-4402; doi:10.3390/nu7064383

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

1
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
2
China National Clinical Research Center for Neurological Diseases, Beijing 100050, China
3
Laborotary of Clinical Medicine Research, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
4
Medical Experiments and Testing Center, Capital Medical University, Beijing 100069, China
5
Department of Pharmacology, School of Chemical Biology & Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China
*
Authors to whom correspondence should be addressed.
Received: 12 April 2015 / Revised: 17 May 2015 / Accepted: 21 May 2015 / Published: 2 June 2015
(This article belongs to the Special Issue Natural Products for Human Health)
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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-κB signal transduction and the subsequent suppression of MMP-2 expression. View Full-Text
Keywords: glioblastoma-initiating cells; RES; invasion; PI3K/Akt; NF-κB; MMP-2 glioblastoma-initiating cells; RES; invasion; PI3K/Akt; NF-κB; MMP-2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Jiao, Y.; Li, H.; Liu, Y.; Guo, A.; Xu, X.; Qu, X.; Wang, S.; Zhao, J.; Li, Y.; Cao, Y. Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-κB Signaling Pathway. Nutrients 2015, 7, 4383-4402.

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