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

Nutrients

Yuming Jiao⁴  Hao Li⁴  Yaodong Liu⁴  Anchen Guo¹  Xiaoxue Xu²  Xianjun Qu³  Shuo Wang⁴  Jizong Zhao⁴  Ye Li³ 

[1] China National Clinical Research Center for Neurological Diseases, Beijing 100050, China; E-Mail:;Medical Experiments and Testing Center, Capital Medical University, Beijing 100069, China; E-Mail:;Department of Pharmacology, School of Chemical Biology & Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China; E-Mail:;Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; E-Mails:

关键词: glioblastoma-initiating cells;    RES;    invasion;    PI3K/Akt;    NF-κB;    MMP-2;   

DOI  :  10.3390/nu7064383

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.