RRC ID 1281
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.
Journal Anticancer Res.
Abstract 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.
Volume 23(2B)
Pages 1395-9
Published 2003-3
PMID 12820400
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
IF 1.865
Times Cited 11
Human and Animal Cells NIH3T3-3