title: Ginsenoside Rh2 inhibits metastasis of glioblastoma multiforme through Akt-regulated MMP13.
abstract: Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor. Although the growth of the tumor cells in a relatively closed space may partially account for its malignancy, highly invasive nature of glioblastoma cells has been suggested to be the main reason for the failure of current therapeutic approaches. Ginsenoside Rh2 (GRh2) has recently been shown to significantly suppress the growth and survival of GBM through inhibiting epidermal growth factor receptor signaling, whereas its effects on the invasion and metastasis have not been examined. Here, we showed that GRh2 dose-dependently decreased GBM cell invasiveness in both scratch wound healing assay and Transwell cell migration assay. Moreover, the inhibitory effects of GRh2 on cell migration seemed to be conducted through decreased expression of matrix metalloproteinase (MMP)-13. Furthermore, using specific inhibitors, we found that GRh2 inhibited MMP13 through PI3k/Akt signaling pathway. Finally, high MMP13 levels were detected in GBM specimen from the patients. Together, these data suggest that GRh2 may suppress GBM migration through inhibiting Akt-mediated MMP13 activation. Thus, our data highlight a previous unappreciated role for GRh2 in suppressing GBM cell metastasis.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Jinzhou, 121001, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Guan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Jinzhou, 121001, China.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Huo
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Jinzhou, 121001, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Jinzhou, 121001, China.
authors.forename: Shoudan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Jinzhou, 121001, China.
authors.forename: Junsheng
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Jinzhou, 121001, China. wenshi_guo@163.com.
authors.forename: Wenshi
authors.initials: W
authors.lastname: Guo
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage*; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D051058:Oncogene Protein v-akt / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D014945:Wound Healing
chemical_list: D036145:Ginsenosides; C055305:ginsenoside Rh2; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
keywords: Akt; Ginsenoside Rh2 (GRh2); Glioblastoma multiforme (GBM); Matrix metalloproteinase (MMP)-13; PI3k
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