Abstract:
AIM:To investigate the effect of 7-hydroxystaurosporine (UCN-01), a selective protein kinase C (PKC) inhibitor, on cell growth, migration, and invasion in invasive human glioblastoma U-87MG cells. METHODS:PKC activity was determined based on the PKC-catalyzed transfer of the (32)P-phosphate group from [g-(32)P]ATP into a PKC-specific peptide substrate. Cell viability was measured by MTT assay. Cell invasion and migration were evaluated by a Boyden chamber assay and scratch wound assay, respectively. Protein expression was analyzed using Western blot assay. The formation of 3-dimensional cellular aggregates was examined by a cell-cell aggregation assay. RESULTS:UCN-01 treatment resulted in concentration- and time-dependent inhibition of U-87MG cell growth at higher doses (>100 nmol/L), and reduced cell invasion and migration capability at less cytotoxic doses (<100 nmol/L). UCN-01 significantly repressed PKC activity. Consistent with this result, UCN-01 blocked cell invasion stimulated by phorbel 12-myristate-13-acetate (PMA) and ethanol (EtOH), 2 PKC activators. Enforced expression of the tumor suppressor genes BRCA1 and PTEN increased the anti-invasion potential of UCN-01. Exposure to UCN-01 caused a dose-dependent increase in cell adhesion molecule E-cadherin. The effect of UCN-01 on the formation of cell-cell aggregation was significantly reduced by the addition of an anti-E-cadherin antibody. CONCLUSION:UCN-01 inhibits the invasion and migration of human glioma cells. Accordingly, UCN-01 can have potential clinical applications for the treatment of human glioma metastasis.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Meng QH,Zhou LX,Luo JL,Cao JP,Tong J,Fan SJdoi
10.1111/j.1745-7254.2005.00087.xsubject
Has Abstractpub_date
2005-04-01 00:00:00pages
492-9issue
4eissn
1671-4083issn
1745-7254journal_volume
26pub_type
杂志文章abstract:AIM:Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo. METHODS:Cell proliferation, DNA fragmentation, Ann...
journal_title:Acta pharmacologica Sinica
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doi:
更新日期:2002-12-01 00:00:00
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更新日期:2002-07-01 00:00:00
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更新日期:2011-10-01 00:00:00
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更新日期:2020-10-01 00:00:00
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更新日期:2001-05-01 00:00:00
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