Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration

<正> Aim:To investigate the effect of 7-hydroxystaurosporine（UCN-01）,a selectiveprotein kinase C（PKC）inhibitor,on cell growth,migration,and invasion in inva-sive human glioblastoma U-87MG cells.Methods:PKC activity was determinedbased on the PKC-catalyzed transfer of the 32p-phosphate group from[g-32p]ATPinto a PKC-specific peptide substrate.Cell viability was measured by MTT assay.Cell invasion and migration were evaluated by a Boyden chamber assay andscratch wound assay,respectively.Protein expression was analyzed using West-ern blot assay.The formation of 3-dimensional cellular aggregates was examinedby a cell-cell aggregation assay.Results:UCN-01 treatment resulted in concen-tration-and time-dependent inhibition of U-87MG cell growth at higher doses（>100 nmol/L）,and reduced cell invasion and migration capability at less cytotoxicdoses（<100 nmol/L）.UCN-01 significantly repressed PKC activity.Consistentwith this result,UCN-01 blocked cell invasion stimulated by phorbel 12-myristate-13-acetate（PMA）and ethanol（EtOH）,2 PKC activators.Enforced expression ofthe tumor suppressor genes BRCA1 and PTEN increased the anti-invasion poten-tial of UCN-01.Exposure to UCN-01 caused a dose-dependent increase in celladhesion molecule E-cadherin.The effect of UCN-01 on the formation of cell-cellaggregation was significantly reduced by the addition of an anti-E-cadherinantibody.Conclusion:UCN-01 inhibits the invasion and migration of humanglioma cells.Accordingly,UCN-01 can have potential clinical applications for thetreatment of human glioma metastasis.