Reference - Detail
|Author||Nakamura K, Yoshikawa N, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M.|
|Title||Effect of PKC412, an inhibitor of protein kinase C, on spontaneous metastatic model mice.|
We investigated the anti-metastatic effect of PKC412, a selective inhibitor of protein kinase C (PKC), on a spontaneous metastatic mouse model, which was prepared by inoculation with B16-BL6 mouse melanoma cells into the footpad of the right hind leg. At two weeks after inoculation, the primary tumor was amputated completely. PKC412 (200 mg/kg) administered orally for four weeks after the tumor inoculation, significantly prolonged survival compared with the control. Furthermore, to elucidate the mechanism of the anti-metastatic effect of PKC412, we examined the growth rate of B16-BL6 cells premixed with Matrigel in vivo and the invasiveness of B16-BL6 cells using a chemo-invasion chamber in vitro. PKC412 significantly reduced the growth rate of cells in vivo (100 and 200 mg/kg) and the invading cells in vitro (10, 30 and 100 nM) in a dose-dependent manner. Thus, PKC412 exerts an anti-metastatic action through inhibition of the invasiveness of melanoma cells in the extracellular matrix.
|MeSH||Administration, Oral Animals Antineoplastic Agents / administration & dosage Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use* Cell Division Collagen Drug Combinations Drug Screening Assays, Antitumor Enzyme Inhibitors / administration & dosage Enzyme Inhibitors / pharmacology Enzyme Inhibitors / therapeutic use* Extracellular Matrix Female Laminin Melanoma, Experimental / drug therapy Melanoma, Experimental / secondary Mice Mice, Inbred C57BL Neoplasm Invasiveness Neoplasm Metastasis / drug therapy* Neoplasm Proteins / antagonists & inhibitors* Neoplasm Transplantation Protein Kinase C / antagonists & inhibitors* Proteoglycans Specific Pathogen-Free Organisms Staurosporine / administration & dosage Staurosporine / analogs & derivatives* Staurosporine / pharmacology Staurosporine / therapeutic use* Tumor Cells, Cultured / drug effects Tumor Cells, Cultured / pathology Tumor Cells, Cultured / transplantation|
|Human and Animal Cells||NIH3T3-3|