Schisandrin B suppresses glioma cell metastasis mediated by inhibition of mTOR/MMP-9 signal pathway.
BACKGROUND
Malignant glioma is the aggressive tumor in the brain and is characterized by high morbidity, high mortality. The main purpose of the present study was to investigate the therapeutic effects of Schisandrin B on glioma cells and preliminary explore the possible mechanism underlying anti-metastasis of Schisandrin B.


METHODS
Two glioma cell lines, U251 and U87, were used in present study. The ability of metastasis of glioma cells was evaluated using transwell migration assay and invasion assay. Expression of Akt, mTOR, MMP-2 and MMP-9 was determined using Western blotting. Antagonist or agonist was used to activated or inactivated signal molecules.


RESULTS
Schisandrin B suppressed cell migration and invasion in manner of dose dependent as well as inhibited expression of p-Akt, p-mTOR and MMP-9. Activation of PI3K by 740Y-P treatment leaded to upregulation of p-Akt, mTOR and MMP-9; inactivation of mTOR by Rapamycin treatment inhibited expression MMP-9 while activation of mTOR by l-Leucine treatment enhanced MMP-9 expression in Schisandrin B incubated cells. Anti-migration and invasion action of Schisandrin B was also reversed by mTOR activation.


CONCLUSIONS
Our findings demonstrate that Schisandrin B can suppress migration and invasion of glioma cell via PI3K/Akt-mTOR-MMP-9 signaling pathway.
Department of Neurosurgery, The Affiliated Hospital of Inner Mongolia National University, Tongliao, Inner Mongolia 028007, China.
Yan
Y
Jiang
Department of Neurosurgery, The Affiliated Hospital of Inner Mongolia National University, Tongliao, Inner Mongolia 028007, China.
Qiuli
Q
Zhang
Department of Neurosurgery, The Affiliated Hospital of Inner Mongolia National University, Tongliao, Inner Mongolia 028007, China.
Jinsuo
J
Bao
Department of Neurosurgery, The Affiliated Hospital of Inner Mongolia National University, Tongliao, Inner Mongolia 028007, China. Electronic address: Du_chua@163.com.
Chenghua
C
Du
Department of Neurosurgery, The Affiliated Hospital of Inner Mongolia National University, Tongliao, Inner Mongolia 028007, China.
Jian
J
Wang
Department of Neurosurgery, The Affiliated Hospital of Inner Mongolia National University, Tongliao, Inner Mongolia 028007, China.
Qiang
Q
Tong
Department of Neurosurgery, The Affiliated Hospital of Inner Mongolia National University, Tongliao, Inner Mongolia 028007, China.
Chang
C
Liu
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D034242:Cyclooctanes / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D034242:Cyclooctanes; D017705:Lignans; D020780:Matrix Metalloproteinase 9; D019869:Phosphatidylinositol 3-Kinases; D011083:Polycyclic Compounds; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C015499:schizandrin B; C546842:MTOR protein, human
Akt; Cell invasion; Cell migration; PI3K; mTOR