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  • Title: Effect of PKC412, an inhibitor of protein kinase C, on spontaneous metastatic model mice.
    Author: Nakamura K, Yoshikawa N, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M.
    Journal: Anticancer Res; 2003; 23(2B):1395-9. PubMed ID: 12820400.
    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.
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