| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
(Purpose) To elucidate the mechanism of growth inhibition by vitamin K2 in hepatoma cells, we examined how apoptosis- and cell cycle-related factors were influenced by vitamin K2.
(Methods) Using human hepatoma cell lines, HepG2, Hep 3B and Huh7, we tested about 1)induction of apoptosis and cell proliferation, 2)cell cycle, 3)expression of cyclin dependent kinase (CDK) inhibitors (p16, p21, p27), 4)expression of cyclin D1, 5)activation of cyclin D1 promoter, 6)binding activity of transcription factors (AP-1, NF-κB) to cyclin D1 promoter, 7)additive effect of anti-cancer agents (CDDP, 5-FU, VP-16, Docetaxel), 8)expression of matrix metalloproteinase (MMP-1, MMP-3, MMP-7), by addition of vitamin K2.
(Results) 1)Vitamin K2 suppressed cell growth, but could not induce apoptosis, 2)vitamin K2 induced G1 arrest, 3)vitamin K2 increase the expression of CDK inhibitors, 4)vitamin K2 decrease the expression of cyclin D1, 5)vitamin K2 decrease promoter activity of cyclin D1, 6)vitamin K2 decrease binding activity of AP-1 and NF-κB to promoter region of cyclin D1, 7)vitamin K2 counteracts the action of CDDP, but enhances the suppressive effect on cell growth of 5-FU, VP-16 and Docetaxel, 8)vitamin K2 inhibits the expression of MMP-1, MMP-3 and MMP-7.
(Conclusion) Vitamin K2 can induce G1 arrest in hepatoma cells by suppression of cyclin D1 expression through inhibition of transcription factor, NF-κB binding to cyclinD1 promoter as well as enhancement of CDK inhibitors expression. Furthermore, these results suggest the possibility on clinical application of vitamin K2 in the field of concomitant treatment with anti-cancer agents and suppression of tumor invasion.
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