Inhibition of migration of human glioblastoma cells by cerivastatin in association with focal adhesion kinase (FAK).
To investigate the biological effect of cerivastatin on glioblastoma cells, we exposed them to various concentrations of cerivastatin. Cerivastatin exhibited dual effects on glioblastoma cells in a dose-dependent manner. Immunofluorescence microscopy showed disruption of actin stress fibers and focal adhesion plaques even at nanomolar concentrations. Matrigel assay demonstrated marked inhibition of glioblastoma cell invasion. Immunoblot analysis using a phosphospecific antibody against focal adhesion kinase (FAK) showed that inhibition of migration was associated with the down-regulation of tyrosine phosphorylation of FAK. Our data suggest that cerivastatin may be beneficial for combination therapy with conventional anti-cancer drugs by inhibiting the invasion of glioblastoma.
Obara
Soichi
S
Department of Neurosurgery, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan. sochian@ta2.so-net.ne.jp
Nakata
Masanori
M
Takeshima
Hideo
H
Kuratsu
Jun-ichi
J
Maruyama
Ikuro
I
Kitajima
Isao
I
D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction / Q000187:drug effects; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000187:drug effects; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007797:Laminin; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000502:physiology*; D011509:Proteoglycans; D011725:Pyridines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D022502:Stress Fibers / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; D011725:Pyridines; C059485:matrigel; D003094:Collagen; C086276:cerivastatin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human