title: Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-κB 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-κB signal transduction and the subsequent suppression of MMP-2 expression.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. shengxiongyuming@163.com.|China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. shengxiongyuming@163.com.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. handanlihao-1@163.com.|China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. handanlihao-1@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. liuyaodong666@sina.com.|China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. liuyaodong666@sina.com.
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. guoanchen@hotmail.com.|Laborotary of Clinical Medicine Research, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. guoanchen@hotmail.com.
authors.forename: Anchen
authors.initials: A
authors.lastname: Guo
authors.affiliation: Medical Experiments and Testing Center, Capital Medical University, Beijing 100069, China. tachee@sina.com.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Chemical Biology & Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China. quxj@ccmu.edu.cn.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. captain9858@vip.sina.com.|China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. captain9858@vip.sina.com.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. guoanchen@hotmail.com.|China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. guoanchen@hotmail.com.
authors.forename: Jizong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Chemical Biology & Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China. yli@ccmu.edu.cn.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. caoyong6@hotmail.com.|China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. caoyong6@hotmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives; D015536:Down-Regulation; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D000077204:Temozolomide
chemical_list: D016328:NF-kappa B; D013267:Stilbenes; D003606:Dacarbazine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D000077185:Resveratrol; D000077204:Temozolomide
keywords: MMP-2; NF-κB; PI3K/Akt; RES; glioblastoma-initiating cells; invasion