Effect of PKC412, an inhibitor of protein kinase C, on spontaneous metastatic model mice.

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.
Authors	Kazuki Nakamura, Noriko Yoshikawa, Yu Yamaguchi, Satomi Kagota, Kazumasa Shinozuka, Masaru Kunitomo
Journal	Anticancer research (Anticancer Res) 2003 Mar-Apr Vol. 23 Issue 2B Pg. 1395-9 ISSN: 0250-7005 [Print] Greece
PMID	12820400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Drug Combinations Enzyme Inhibitors Laminin Neoplasm Proteins Proteoglycans matrigel Collagen Protein Kinase C Staurosporine midostaurin
Topics	Administration, Oral Animals Antineoplastic Agents (administration & dosage, pharmacology, therapeutic use) Cell Division Collagen Drug Combinations Drug Screening Assays, Antitumor Enzyme Inhibitors (administration & dosage, pharmacology, therapeutic use) Extracellular Matrix Female Laminin Melanoma, Experimental (drug therapy, 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, analogs & derivatives, pharmacology, therapeutic use) Tumor Cells, Cultured (drug effects, pathology, transplantation)

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